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1.
Artigo em Chinês | MEDLINE | ID: mdl-34074073

RESUMO

Objective: To investigate the effects of rapamycin target protein (mTOR) pathway and autophagy on bone formation and bone resorption in fluorosis osteoporosis in rats. Methods: In September 2018, a rat model of skeletal fluorosis was established by intragastric administration of fluorine. The experimental animals were divided into control group, 10 mgF(-)/kg group, 20 mgF(-)/kg group, 2 mg/kg rapamycin (RAPA) +10 mgF(-)/kg group and 2 mg/kg RAPA+20 mgF(-)/kg group, 20 per group. The experiment lasted for 3 months. The changes of bone tissue in rats were observed by hematoxylin-eosin (HE) staining. Bone mineral density (BMD) and biomechanical indexes, such as Modulus of elasticity, Stiffness, Maximum stress and Maximum load, were measured by BMD and biomechanical biometer. Serum levels of alkaline phosphatase (ALP) , osteocalcin (BGP) , osteoprotectin (OPG) , type I procollagen amino-terminal peptide (PINP) , tartrate-resistant acid phosphatase (TRACP) and nuclear factor kappa B receptor activator ligand (RANKL) were determined by enzymatic linked immunosorbent assay (ELISA) . Bone tissue phosphorylated mTOR (p-mTOR) , autophagy-related index selective autophagy adaptor protein p62, microtubule associated protein II (LC3-II) , ALP, osteoblastic transcription factor (Osterix) , and RNT Expression of related transcription factor 2 (Runx2) and bone resorption indicator RANKL were detected by Western blotting. Results: Compared with the control group, dental fluorosis in the 10 mgF(-)/kg and 20 mgF(-)/kg groups was significantly increased, periosteum thickness and absorption lacunae appeared, and BGP, OPG, PINP, TRACP and RANKL in serum contents were increased (P<0.05) , BMD, Modulus of elasticity, Stiffness, Maximum stress and Maximum load of bone tissue decreased significantly (P<0.05) , and the expressions of p-mTOR and p62 were decreased (P<0.05) , also the expressions of ALP, Osterix, Runx2 and RANKL were increased (P<0.05) . Compared with 10 mgF(-)/kg and 20 mgF(-)/kg groups, there were no obvious dental fluorosis symptoms in 2 mg/kg RAPA+10 mgF(-)/kg group and 2 mg/kg RAPA+20 mgF(-)/kg group, and serum ALP, BGP and OPG levels were significantly increased (P<0.05) . TRACP and RANKL contents were significantly decreased (P<0.05) . BMD, Modulus of elasticity, Stiffness, Maximum stress and Maximum load were significantly increased (P<0.05) . The levels of p-mTOR, p62 and RANKL in bone tissues were decreased (P<0.05) , and the expressions of LC3-II, LC3-II/LC3-I, ALP, Osterix and Runx2 were increased (P<0.05) . Conclusion: RAPA may activate autophagy by inhibiting mTOR phosphorylation, and inhibit bone resorption while promoting bone formation, thus alleviating early osteoporosis in skeletal fluorosis rats.


Assuntos
Autofagia , Osteoporose , Sirolimo , Serina-Treonina Quinases TOR , Animais , Densidade Óssea , Flúor/efeitos adversos , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Ratos , Ratos Sprague-Dawley
2.
BMC Musculoskelet Disord ; 22(1): 519, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090401

RESUMO

BACKGROUND: Dehydroepiandrosterone (DHEA), an adrenal steroid, has a protective role against diabetes. This study aimed to investigate the in vitro and in vivo protective effects of DHEA against high glucose-induced oxidative stress in tenocytes and tendons. METHODS: Tenocytes from normal Sprague-Dawley rats were cultured in low-glucose (LG) or high-glucose (HG) medium with or without DHEA. The experimental groups were: control group (LG without DHEA), LG with DHEA, HG without DHEA, and HG with DHEA. Reactive oxygen species (ROS) production, apoptosis, and messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, and interleukin-6 (IL-6) were determined. Further, diabetic rats were divided into a control group and a DHEA-injected group (DHEA group). NOX1 and NOX4 protein expression and mRNA expression of NOX1, NOX4, IL-6, matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-2, and type I and III collagens in the Achilles tendon were determined. RESULTS: In rat tenocytes, DHEA decreased the expression of NOX1 and IL-6, ROS accumulation, and apoptotic cells. In the diabetic rat Achilles tendon, NOX1 protein expression and mRNA expression of NOX1, IL-6, MMP-2, TIMP-2, and type III collagen were significantly lower while type I collagen expression was significantly higher in the DHEA group than in the control group. CONCLUSIONS: DHEA showed antioxidant and anti-inflammatory effects both in vitro and in vivo. Moreover, DHEA improved tendon matrix synthesis and turnover, which are affected by hyperglycemic conditions. DHEA is a potential preventive drug for diabetic tendinopathy.


Assuntos
Diabetes Mellitus Experimental , Tenócitos , Animais , Células Cultivadas , Desidroepiandrosterona/farmacologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Glucose/toxicidade , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley
3.
J Biomed Nanotechnol ; 17(5): 942-951, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34082879

RESUMO

Naringenin (NGN) can be used to inhibit the progression of nonalcoholic fatty liver disease (NAFLD) in mice, but its poor water solubility limits its applications. Nanostructured lipid carriers (NLCs) have recently attracted much attention in the field of nanodrug delivery systems because they increase the drug loading capacity and impressively enhance the solubility of indissolvable drugs. Herein, a thin-film dispersion method was used to prepare naringenin-loaded nanostructured lipid carriers (NGN-NLCs). These NGN-NLCs have a narrow size distribution of 171.9 ±2.0 nm, a high drug loading capacity of 23.7 ± 0.3%, a high encapsulation efficiency of 99.9 ± 0.0% and a drug release rate of 86.2 ± 0.4%. NGN- NLCs elevated the pharmacokinetic parameters (Cmax and AUC0→t) of NGN, accelerated NGN transepithelial transport in MDCK cells and intestinal absorption in the jejunum and ileum, and reduced hepatic lipid accumulation in an oleic acid (OA) plus lipopolysaccharide (LPS)-induced lipid deposition cell model in primary hepatocytes and in a methionine/choline deficient (MCD) diet-induced NAFLD mouse model. A detailed study of the mechanism showed that this NLC formulation elevated the drug release rate in simulated intestinal solutions in vitro, the transepithelial transport in MDCK cells, the oral absorption in mice and the ex vivo intestinal absorption of NGN. Thus, NGN-NLCs significantly enhanced the inhibitory effects of NGN on MCD diet induced mouse NAFLD.


Assuntos
Nanoestruturas , Hepatopatia Gordurosa não Alcoólica , Administração Oral , Animais , Portadores de Fármacos , Flavanonas , Lipídeos , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley
4.
Zhen Ci Yan Jiu ; 46(5): 362-7, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085457

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture(EA) intervention on the behavior, colon and midbrain substantia nigra α-synuclein(α-syn) expression in Parkinson's disease (PD) mice, so as to explore the mechanism of early EA on prevention of PD. METHODS: C57BL/6J mice were randomly divided into blank, model and EA groups, with 8 mice in each group. The PD mouse model was established by subcutaneous injection of rotenone. Mice in the EA group received EA (2 Hz, 1 mA) at "Quchi"(LI11), "Shangjuxu"(ST37) and acupuncture at "Shenting" (GV24)and "Tianshu"(ST25) for 10 min once daily, with 7 d for a course, a total of 8 courses. Behavioral tests of hanging and climbing poles were carried out before, during and after modeling. The expressions of a-syn in substantia nigra and colon were detected by Western blot and immunohistochemistry or immunofluorescence. RESULTS: After 8 weeks of modeling, the mice in the model group showed symptoms such as listlessness, dim hair color, coldness and curling up. Compared with the blank group, the hanging score of the model group was significantly lower (P<0.01), the pole climbing time and the expressions of α-syn protein in colon and substantia nigra were significantly increased (P<0.01). Following intervention, mice in the EA group were always in good mental state, with shiny fur and stable body weight. The hanging scores was significantly higher and the pole climbing time and the expressions of α-syn protein in colon and substantia nigra were significantly down-regulated (P<0.05, P<0.01) in the EA group relevant to the model group. CONCLUSION: Early EA intervention can delay the onset of PD induced by rotenone, which may be related to its effect in reducing the expression of α-syn in midbrain substantia nigra and colon.


Assuntos
Eletroacupuntura , Doença de Parkinson , Animais , Colo , Camundongos , Camundongos Endogâmicos C57BL , Doença de Parkinson/genética , Doença de Parkinson/terapia , Ratos , Ratos Sprague-Dawley , Substância Negra
5.
Zhen Ci Yan Jiu ; 46(5): 375-9, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085459

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Ciliao" (BL32) and "Huiyang" (BL35) on the expression of extracellular signal-regulated kinase 1/2 (p-ERK1/2) and cellular oncogene fos (c-fos) phosphorylated of spinal dorsal horn in rats with interstitial cystitis (IC). METHODS: Eighteen female Wistar rats were randomly divided into control, model and EA groups, with 6 rats in each group. The IC model was established by intraperitoneal injection of cyclophosphamide (150 mg/kg). EA (30 Hz, 1 mA) was applied to bilateral BL32 and BL35 for 20 min, once daily for 3 consecutive days. The bladder pain was measured by using a Von Frey at 48 h after modeling and 24 h after EA. The expression levels of p-ERK1/2 and c-fos protein in L6-S1 segment of spinal cord were detected by Western blot, and the expression of p-ERK1/2 and c-fos in the right spinal dorsal horn were displayed by immunofluorescence staining. RESULTS: After modeling, the bladder mechanical pain threshold (PT) was significantly decreased (P<0.05), the protein expression of p-ERK1/2 and c-fos in the spinal cord was increased (P<0.05) and the immunofluorescence surface density of p-ERK1/2 and c-fos in the right dorsal horn of spinal cord was increased (P<0.05) in the model group relevant to the control group. After EA intervention, IC-induced reduction of PT, and increases of the expression of p-ERK1/2 and c-fos as well as immunofluorescence surface density of p-ERK1/2 and c-fos were reversed in the EA group relevant to the model group (P<0.05). CONCLUSION: EA at BL 32 and BL 35 has an analgesic effect in IC rats, which may be related to its effect in down-regulating the expression of p-ERK1/2 and c-fos in spinal dorsal horn.


Assuntos
Cistite Intersticial , Eletroacupuntura , Animais , Feminino , Sistema de Sinalização das MAP Quinases , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Medula Espinal/metabolismo , Corno Dorsal da Medula Espinal/metabolismo
6.
Zhen Ci Yan Jiu ; 46(5): 380-4, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085460

RESUMO

OBJECTIVE: To observe the effect of acupoint catgut embedding (ACE) combined with moxibustion on the expressions of Notch receptor 1 and target genes Hes 1 and Math 1 in colonic mucosa of ulcerative colitis (UC) rats, so as to reveal its mechanism of treating UC from the perspective of Notch signaling pathway. METHODS: Thirty SD rats were randomized into normal, model, ACE combined with moxibustion (combination), ACE, and moxibustion groups (n=6 in each group). The UC model was established by intrarectal administration of 5% trinitro-benzene-sulfonic acid and 50% ethyl alcohol. Moxibustion was applied to bilateral "Shangjuxu" (ST37), "Tianshu" (ST25) and "Dachangshu" (BL25) for 10 min, once daily for 14 days, and ACE applied to the same 3 acupoints, once a week for two weeks. After the treatment, colonic mucosal pathological changes were observed after hematoxylin eosin (HE) stain. Protein and mRNA expressions of Notch 1, Hes 1 and Math 1 were detected by RT-PCR and Western blot, respectively. RESULTS: H.E. staining showed severe defect of the colonic mucosal epithelium with infiltration of a large number of inflammatory cells in the model group, which was milder in moxibustion, ACE and moxibustion + ACE groups. After modeling, the protein and mRNA expressions of Notch 1 and Hes 1 in the colonic mucosa were obviously increased (P<0.01), while the protein and mRNA expressions of Math 1 were significantly decreased (P<0.01) in the model group relevant to the normal group. Following the intervention, the protein and mRNA expression levels of Notch 1 and Hes 1 in the colonic mucosa were significantly lower (P<0.05, P<0.01) in moxibustion, ACE and combination groups, the mRNA expression level of Math 1 was significantly increased in both ACE and combination groups (P<0.01), and the protein expression of Math 1 was significantly higher in the three treatment groups relevant to the model group (P<0.01). The above indexes of moxibustion + ACE were considerably superior to those of simple ACE and simple moxibustion (P<0.05, P<0.01). CONCLUSION: Acupoint catgut embedding combined with moxibustion can repair the injured colonic mucosa of UC rats, which may be related with its effects in suppressing the expression of Notch 1 and Hes 1, up-regulating the expression of Math 1 in the colonic mucosa, thereby regulating the balance of differentiation between colonic epithelial secretory and absorption cell lines.


Assuntos
Colite Ulcerativa , Moxibustão , Pontos de Acupuntura , Animais , Categute , Colite Ulcerativa/genética , Colite Ulcerativa/terapia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
7.
Zhen Ci Yan Jiu ; 46(5): 385-90, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085461

RESUMO

OBJECTIVE: To investigate the effect of joint administration of electroacupuncture (EA) and bone marrow mesenchymal stem cells (BMMSC) on the expression of estrogen receptor (ER) and progesterone receptor (PR) in thin endometrium rats, so as to explore its mechanisms underlying improvement of conception rate. METHODS: Forty female SD rats were divided into control, model, BMMSC and EA+BMMSC groups. The thin endometrium model was established by intrauterine infusion of 95% ethanol and saline. EA (1 mA, 2 Hz/15 Hz) was applied to "Guanyuan"(CV4), unilateral "Zigong" (EX-CA1) and unila-teral "Sanyinjiao" (SP6) for 15 min, once daily for 10 d. Rats of the BMMSC and EA+BMMSC groups received injection of BMMSC suspension through caudal vein on the day of modeling, the 3rd day after surgery, and the 2nd and the 3rd estrus phases, respectively. Changes of body weight and estrus phase were continuously recorded. After three estrus cycles, uterine specimens were taken and the uterine coefficient was calculated. The immunoactivity of KI67(an antigen for cell proliferation) was detected by immunohistochemistry, and the expression of ER and PR was detected by Western blot. RESULTS: Compared with the control group, the uterine coefficient, and expression of endometrium ER and PR proteins were significantly decreased in the model group (P<0.001, P<0.01). In Comparison with the model group, the uterine coefficient, immunoactivity of KI67, and expression of ER and PR proteins were significantly increased in both BMMSC and EA+BMMSC groups (P<0.000 1,P<0.001, P<0.01). The expression level of PR in the EA+BMMSC group was notably higher than that in the BMMSC group (P<0.05), but no significant difference was found between the BMMSC and EA+BMMSC groups in the levels of uterine coefficient and ER expression (P>0.05). CONCLUSION: EA combined with BMMSC injection has a positive effect in promoting the proliferation of endometrium cells in rats with thin endometrium, which may be related to its effect in up-regulating the expression of ER and PR proteins.


Assuntos
Eletroacupuntura , Células-Tronco Mesenquimais , Pontos de Acupuntura , Animais , Endométrio , Feminino , Ratos , Ratos Sprague-Dawley , Receptores Estrogênicos/genética , Receptores de Progesterona/genética
8.
Zhen Ci Yan Jiu ; 46(5): 397-403, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085463

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Weizhong" (BL40) on the expression of platelet-derived growth factor (PDGF)-CC, PDGF receptor (PDGFR)α and matrix metalloproteinase-1 (MMP-1) in rats with lumbar multifidus muscle injury (LMMI) so as to study its mechanisms underlying improvement of skeletal muscle injury. METHODS: Fifty-four male SD rats were randomly divided into normal group (n=6), model group (n=24) and EA group (n=24), and the latter two groups were further divided into four subgroups (1, 3, 5 and 7 days), with 6 rats in each group. The LMMI model was established by injection of 0.5% bupivacaine (BPVC, 100 µL×4) into the multifidus along the L4 and L5 spinous process. EA (2 Hz/50 Hz, 1 mA) was applied to bilateral "Weizhong"(BL40) for 20 min, once daily for 1, 3, 5 and 7 days respectively, from the first day on after modeling. Histopathological changes of the left multifidus muscle were observed after H.E. staining, and the expression of PDGF-CC, PDGFR-α and MMP-1 proteins in the right multifidus was observed by Western blot. RESULTS: Compared with the normal group, the expression levels of PDGF-CC protein in the model subgroup 1 d, 3 d and 7 d were significantly decreased (P<0.05), and those of PDGFR-α and MMP-1 proteins in the model subgroup 5 d and 7 d, and PDGF-CC protein in the model subgroup 5 d significantly increased (P<0.05). In comparison with the model subgroups, the expression levels of PDGF-CC in the EA subgroup 3 d, 5 d and 7 d, PDGFR-α in the EA subgroup 5 d, and MMP-1 in the EA group 3 d and 5 d were significantly increased or significantly further increased (P<0.05). H.E. staining showed different shapes and uneven sizes, with large area of damage, enlarged muscle space and inflammatory cell infiltration in the model group, which was relatively milder in the EA subgroups particularly in subgroup 5 d and 7 d. CONCLUSION: EA stimulation of BL40 for about 5 days has a positive effect in promoting the repair of the injured multifidus muscle in LMMI rats, which may be related to its function in up-regulating the expression of muscular PDGF-CC, PDGFR-α and MMP-1 proteins.


Assuntos
Eletroacupuntura , Animais , Linfocinas , Masculino , Metaloproteinase 1 da Matriz/genética , Músculos Paraespinais , Fator de Crescimento Derivado de Plaquetas/genética , Ratos , Ratos Sprague-Dawley , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética
9.
Zhen Ci Yan Jiu ; 46(5): 404-10, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085464

RESUMO

OBJECTIVE: To compare the effect of electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS) of skin and muscle layers of "Liangqiu" (ST34) area on inflammatory muscular pain in rats, so as to study the role of different-layer afferent nerve fibers in acupuncture analgesia. METHODS: A total of 120 male SD rats were used in the present study, including 8 rats used for determining the excitatory threshold of Aδ(Ta) and C (Tc) afferent nerve fibers, 48 employed for comparing the analgesic effect of EA and TEAS at intensities of Ta and Tc, and 64 for observing the effect of EA and TAES stimulation of ipsilateral (Ipsi), contralateral (Contra) ST34 and ipsilateral LI4 at Ta and Tc intensities. Inflammatory muscle pain was induced by injection of complete Freund's adjuvant (CFA) into the right biceps femoris muscle. In the second part of the present study, 48 rats were randomly and equally divided into control, model, TEAS-Ta, TEAS-Tc, EA-Ta and EA-Tc groups, while in the 3rd part, 64 rats were randomly and equally divided into control, model, Ipsi-ST34-TEAS, Contra-ST34-TEAS, Ipsi-ST34-EA, Contra-ST34-EA, Ipsi-LI4-TEAS and Ipsi-LI4-EA groups. TEAS or EA was applied to the skin and muscle layers, respectively. Before and after modeling, the animal was forced to stand on a bipedal equilibrator, the difference in body mass distribution of both feet (bearing difference) was used to assess the pain severity. The frequency of myoelectrical discharges of the right bicep femoris muscle in responding to electrical stimulation of the spot between the 4th and 5th toes of the ipsilateral hindlimb at an intensity of two-folds of C-fiber excitatory threshold was recorded. RESULTS: 1) The bearing difference between the bilateral hindlimbs was markedly higher in the model group than in the control group (P<0.01), and significantly lower at the 2nd and 3rd day in the EA-Ta and EA-Tc, and TEAS-Tc groups relevant to the model group (P<0.05, P<0.01). 2) The frequency of C-fiber reflex induced electromyogram (EMG) activities were significantly decreased at 0 and 1 min after TEAS of both ipsilateral ST34 at Tc, and 0 min after TEAS of the contralateral ST34 at Tc (rather than at Ta and not LI4 even at Tc) in comparison with pre-TEAS, and 0, 1 and 2 min after TEAS of ipsilateral ST34 at Tc, and 0 min after TEAS of contra-ST34 at Tc compared with the model group, respectively (P<0.01, P<0.05). In comparison with pre-EA, the frequency of C-fiber reflex induced EMG activities were significantly decreased at 0 and 1 min after EA of the ipsilateral ST34 at Ta, and 0 min after EA of the contra-ST34 at Ta. In addition, the frequency of C-fiber reflex induced EMG activities were decreased at 0, 1 and 2 min after EA of the ipsilateral ST34 at Tc, and 0 and 1 min after EA of the contra-ST34 at Tc, as well as 0 min after EA of LI4 at Tc (P<0.01, P<0.05).In comparison with the model group, the frequency of C-fiber reflex induced EMG activities are significantly decreased at 0, and 1 min after EA of the ipsilateral ST34 at Ta, and 0 min after EA of the contra-ST34 at Ta. In addition, the frequency of C-fiber reflex induced EMG activities were decreased at 0, 1 ,2,and 3 min after EA of the ipsilateral ST34 at Tc, and 0 and 1 min after EA of the contra-ST34 at Tc, as well as 0 min after EA of LI4 at Tc, respectively (P<0.01, P<0.05). CONCLUSION: TEAS-ST34 at Tc and EA-ST34 at both Ta and Tc can alleviate pain behavior in inflammatory pain rats, which may be related to its effect in activating the afferent nerve fiber in different layers of ST34 area.


Assuntos
Eletroacupuntura , Pontos de Acupuntura , Animais , Masculino , Mialgia , Fibras Nervosas , Ratos , Ratos Sprague-Dawley
10.
Zhen Ci Yan Jiu ; 46(5): 411-5, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34085465

RESUMO

OBJECTIVE: To observe the effect of application at Back-Shu with Front-Mu acupoints on serum uric acid (SUA) and kidney uric acid transport related proteins in hyperuricemia rats, so as to explore the mechanism of Shu-Mu acupoint application on treatment of hyperuricemia. METHODS: SD rats were randomly divided into blank control, model, vaseline application and medication application groups, with 8 rats in each group. The hyperuricemia rat model was established by gavage of potassium oxonate. Rats in the vaseline application group received application of vaseline at bilateral "Ganshu"(BL18) and "Qimen"(LI14), "Pishu"(BL20) and "Zhangmen"(LR13), "Shenshu" (BL23) and "Jingmen"(GB25). Rats in the medication application group received application of traditional Chinese medicine at the same acupoints. The contents of SUA and creatinine (SCr) were detected by automatic biochemical analyzer. H.E. staining was used to observe the pathological changes of kidney. And the protein expression levels of organic anion transporter 1(OAT1) and adenosine triphosphate binding cassette transporter G2(ABCG2) were detected by immunohistochemistry. RESULTS: Rats in the model group showed symptoms such as polydipsia, polyuria, loose stools, fatigue, weakness, etc. The renal tubules atrophied, and urate crystals can be seen in the lumen. Compared with the control group. the SUA content in the model group increased (P<0.01)and the expressions of OAT1 and ABCG2 protein in kidney decreased (P<0.01). After intervention and in comparison with the model group showed that, the diet, excretion function, and mental state of the rats in the medication application group returned to normal, and the pathological changes of the kidney tissue were alleviated, the SUA content was down-regulated(P<0.01)and the expression levels of OAT1 and ABCG2 in the kidney up-regulated (P<0.01). There was no statistically significant difference in the SCr content among the 4 groups (P>0.05). CONCLUSION: Medication application at Shu-Mu points can effectively reduce the SUA level of hyperuricemia rats, which may be related to its effects in up-regulating the protein expressions of OAT1 and ABCG2 in the kidney and reducing the damage to the kidneys.


Assuntos
Hiperuricemia , Pontos de Acupuntura , Animais , Hiperuricemia/tratamento farmacológico , Hiperuricemia/genética , Rim , Ratos , Ratos Sprague-Dawley , Ácido Úrico
11.
Zhongguo Zhen Jiu ; 41(6): 651-6, 2021 Jun 12.
Artigo em Chinês | MEDLINE | ID: mdl-34085483

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment on inflammatory reaction, apoptosis and expression of Yes-associated protein (YAP) of ischemic penumbra of cerebral cortex in cerebral ischemia reperfusion injury rats, and to explore the possible mechanism of its neuroprotection effect. METHODS: A total of 84 SD rats were randomized into a sham operation group (12 rats), a model group (18 rats), an EA group (18 rats), an EA+YAP virus transfection group (18 rats) and an EA+virus control group (18 rats). Except for the sham operation group, thread embolization method was adopted to establish the middle cerebral artery occlusion (MCAO) model in rats of the other groups. EA was applied at "Baihui" (GV 20) and "Dazhui" (GV 14) for 30 min in the 3 EA intervention groups 2 h before model establishment, disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in intensity. Adenovirus transfection technique was used to induce gene silencing of YAP in the EA+YAP virus transfection group, and adenovirus vectors was injected as negative control in the EA+virus control group 4 d before model establishment. Twenty-four hours after model establishment, neurological function score was evaluated, the relative cerebral infarction area was observed by TTC staining, the apoptosis in the ischemic penumbra of cerebral cortex was detected by TUNEL staining, the levels of inflammatory factors IL-1ß, IL-6 and TNF-α in the ischemic penumbra of cerebral cortex was detected by ELISA method, the expression of YAP was detected by Western blot and immunofluorescence. RESULTS: Compared with the sham operation group, the expression of YAP was increased in the model group (P<0.05); compared with the model group, the expression of YAP in the ischemic penumbra of cerebral cortex was increased in the EA group (P<0.05). Compared with the sham operation group, the neurological function score, the percentage of TUNEL positive cells and the levels of IL-1ß, IL-6 and TNF-α in the ischemic penumbra of cerebral cortex were increased in the model group (P<0.001, P<0.01); compared with the model group, the neurological function score, the relative cerebral infarction area, the percentage of TUNEL positive cells and the levels of IL-1ß, IL-6 and TNF-α in the ischemic penumbra of cerebral cortex were decreased in the EA group (P<0.05, P<0.01); compared with the EA group, the neurological function score, the relative cerebral infarction area, the percentage of TUNEL positive cells and the levels of IL-1ß, IL-6 and TNF-α in the ischemic penumbra of cerebral cortex were increased in the EA+YAP virus transfection group (P<0.01, P<0.05); compared with the EA+YAP virus transfection group, the neurological function score, the relative cerebral infarction area, the percentage of TUNEL positive cells and the levels of IL-1ß, IL-6 and TNF-α in the ischemic penumbra of cerebral cortex were decreased in the EA+virus control group (P<0.01, P<0.05). CONCLUSION: Electroacupuncture pretreatment can effectively improve the ischemia reperfusion injury, its mechanism may be related to up-regulating the expression of YAP in the ischemic penumbra of cerebral cortex and relieving the apoptosis and inflammatory reaction.


Assuntos
Isquemia Encefálica , Eletroacupuntura , Traumatismo por Reperfusão , Animais , Isquemia Encefálica/genética , Isquemia Encefálica/terapia , Infarto da Artéria Cerebral Média , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/terapia
12.
Acta Cir Bras ; 36(4): e360406, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34076083

RESUMO

PURPOSE: To evaluate the effects of controlled decompression and rapid decompression, explore the potential mechanism, provide the theoretical basis for the clinical application, and explore the new cell death method in intracranial hypertension. METHODS: Acute intracranial hypertension was triggered in rabbits by epidural balloon compression. New Zealand white rabbits were randomly put into the sham group, the controlled decompression group, and the rapid decompression group. Brain water content, etc., was used to evaluate early brain injury. Western blotting and double immunofluorescence staining were used to detect necroptosis and apoptosis. RESULTS: Brain edema, neurological dysfunction, and brain injury appeared after traumatic brain injury (TBI). Compared with rapid decompression, brain water content was significantly decreased, neurological scores were improved by controlled decompression treatment. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and Nissl staining showed neuron death decreased in the controlled decompression group. Compared with rapid decompression, it was also found that apoptosis-related protein caspase-3/ tumor necrosis factor (TNF)-a was reduced markedly in the brain cortex and serum, and the expression levels of necroptosis-related protein, receptor-interacting protein 1 (RIP1)/receptor-interacting protein 1 (RIP3) reduced significantly in the controlled decompression group. CONCLUSIONS: Controlled decompression can effectively reduce neuronal damage and cerebral edema after craniocerebral injury and, thus, protect the brain tissue by alleviating necroptosis and apoptosis.


Assuntos
Lesões Encefálicas , Hipertensão Intracraniana , Animais , Apoptose , Descompressão , Necroptose , Coelhos , Ratos , Ratos Sprague-Dawley
13.
Braz J Med Biol Res ; 54(9): e10842, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34076142

RESUMO

Regeneration of injured peripheral nerves is an extremely complex process. Nogo-A (neurite outgrowth inhibitor-A) inhibits axonal regeneration by interacting with Nogo receptor in the myelin sheath of the central nervous system (CNS). The aim of this study was to investigate the effects of Nogo-A and its receptor on the repair of sciatic nerve injury in rats. Sprague-Dawley rats (n=96) were randomly divided into 4 groups: control group (control), sciatic nerve transection group (model), immediate repair group (immediate repair), and delayed repair group (delayed repair). The rats were euthanized 1 week and 6 weeks after operation. The injured end tissues of the spinal cord and sciatic nerve were obtained. The protein expressions of Nogo-A and Nogo-66 receptor (NgR) were detected by immunohistochemistry. The protein expressions of Nogo-A, NgR, and Ras homolog family member A (RhoA) were detected by western blot. At 1 week after operation, the pathological changes in the immediate repaired group were less, and the protein expressions of Nogo-A, NgR, and RhoA in the spinal cord and sciatic nerve tissues were decreased (P<0.05) compared with the model group. After 6 weeks, the pathological changes in the immediate repair group and the delayed repair group were alleviated and the protein expressions decreased (P<0.05). The situation of the immediate repair group was better than that of the delayed repair group. Our data suggest that the expression of Nogo-A and its receptor increased after sciatic nerve injury, indicating that Nogo-A and its receptor play an inhibitory role in the repair process of sciatic nerve injury in rats.


Assuntos
Proteínas da Mielina , Receptores de Superfície Celular , Animais , Proteínas Ligadas por GPI , Regeneração Nervosa , Proteínas Nogo , Ratos , Ratos Sprague-Dawley , Nervo Isquiático
14.
Mater Sci Eng C Mater Biol Appl ; 126: 112131, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34082948

RESUMO

Investigating axonal myelination by Schwann cells (SCs) is crucial for understanding mechanisms underlying demyelination and remyelination, which may help gain insights into incurable disorders like neurodegenerative diseases. In this study, a gelatin-based hydrogel, gelatin methacryloyl (GelMA), was optimized to achieve the biocompatibility, porosity, mechanical stability, and degradability needed to provide high cell viability for dorsal root ganglia (DRG) neurons and SCs, and to enable their long-term coculture needed for myelination studies. The results of cell viability, neurite elongation, SC function and maturation, SC-axon interaction, and myelination were compared with two other commonly used substrates, namely collagen and Poly-d Lysine (PDL). The tuned GelMA constructs (Young's modulus of 32.6 ± 1.9 kPa and the median value of pore size of 10.3 µm) enhanced single axon generation (unlike collagen) and promoted the interaction of DRG neurons and SCs (unlike PDL). While DRG cells exhibited relatively higher viability on PDL after 48 h, i.e., 83.8%, the cells had similar survival rate on GelMA and collagen substrates, 66.7% and 61.5%, respectively. Further adjusting the hydrogel properties to achieve two distinct ranges of relatively small and large pores supported SCs to extend their processes freely and enabled physical contact with and wrapping around their corresponding axons. Staining the cells with myelin basic protein (MBA) and myelin-associated glycoprotein (MAG) revealed enhanced myelination on GelMA hydrogel compared to PDL and collagen. Moreover, the engineered porosity enhanced DRGs and SCs attachments and flexibility of movement across the substrate. This engineered hydrogel structure can now be further explored to model demyelination in neurodegenerative diseases, as well as to study the effects of various compounds on myelin regeneration.


Assuntos
Gelatina , Hidrogéis , Neurônios , Animais , Células Cultivadas , Colágeno , Gânglios Espinais , Bainha de Mielina , Ratos Sprague-Dawley , Células de Schwann
15.
Zhonghua Nei Ke Za Zhi ; 60(6): 552-555, 2021 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-34058812

RESUMO

To investigate the effects of different fluid resuscitation on renal function and glycocalyx in septic shock rats. The septic shock SD rats (induced by lipopolysaccharide) were randomly divided into control group, normal saline resuscitation group, Lactate Ringer's solution resuscitation group and succinyl gelatin resuscitation group (n=6 each). The mean arterial pressure, heart rate, serum creatinine (Scr), urea nitrogen (BUN), renal blood flow, renal tissue pathology, serum interleukin-6, tumor necrosis factor α and glycocalyx were measured at baseline, the development of septic shock, 0 hour and 8 hours after resuscitation. When shock was established, the renal blood flow significantly decreased (P<0.05) and recovered to normal at 0 hour and 8 hours after resuscitation. Compared with normal saline group and succinyl gelatin group, the levels of Scr, BUN and glycocalyx components (heparan sulfate, syndecan-1) were significant lower in Lactate Ringer's solution group (P<0.05). The pathology of kidney tissue suggested that the microscopic ischemic damage with Lactate Ringer's solution were minor than the other two groups. Compared with normal saline and succinyl gelatin, Lactate Ringer's solution can reduce the damage of renal function and glycocalyx in septic shock rats.


Assuntos
Choque Hemorrágico , Choque Séptico , Animais , Hidratação , Glicocálix , Ratos , Ratos Sprague-Dawley , Choque Hemorrágico/tratamento farmacológico , Choque Séptico/terapia
16.
Food Funct ; 12(9): 4105-4116, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33977918

RESUMO

Epigallocatechin-3-gallate (EGCG) and caffeine constitute the most effective ingredients of weight loss in tea. However, whether combination of EGCG and caffeine exhibits anti-obesity synergy remains unclear. Here, we showed low-doses of EGCG and caffeine used in combination led to synergistic anti-obesity effects equivalent to those of high-dose EGCG. Furthermore, combination treatment exhibited a synergistic effect on altering gut microbiota, including decreased Firmicutes level and increased Bifidobacterium level. Other notable effects of combination treatment included synergistic effects on: increasing fecal acetic acid, propionic acid, and total SCFAs; decreasing expression of GPR43; and increasing microbial bile salt hydrolase gene copies in the gut, facilitating generation of unconjugated BAs and enhancing fecal BA loss. Additionally, combination treatment demonstrated synergistic effects toward increasing the expression of hepatic TGR5 and decreasing the expression of intestinal FXR-FGF15, resulting in increased expression of hepatic CYP7A1. Thus, the synergistic effect may be attributed to regulation of gut microbiota and BA metabolism.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Ácidos e Sais Biliares/metabolismo , Cafeína/administração & dosagem , Catequina/análogos & derivados , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/tratamento farmacológico , Animais , Ácidos e Sais Biliares/análise , Catequina/administração & dosagem , Colesterol 7-alfa-Hidroxilase/metabolismo , Sinergismo Farmacológico , Quimioterapia Combinada , Ácidos Graxos Voláteis/análise , Ácidos Graxos Voláteis/metabolismo , Fezes/química , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo
17.
Food Funct ; 12(9): 3954-3964, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33977937

RESUMO

The therapeutic effects of water extract of ginseng (WEG) on exercise-induced fatigue (EF) have been reported in several previous studies, but the molecular mechanisms involved remain unexplored. In this study, the anti-EF effects of WEG were studied, and the potential mechanisms were discussed. We characterized the chemical components of WEG by ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS) and high performance liquid chromatography coupled with evaporative light scattering detection (HPLC-ELSD), and then examined the anti-EF effects of WEG on a rat model of weight-loaded swimming with a focus on endogenous metabolism and gut microbiota. WEG contains abundant (90.15%, w/w) saccharides and ginsenosides with structurally diverse glycosyls. WEG taken orally showed strong anti-EF effects by ameliorating energy metabolism abnormality, oxidative stress, lipid peroxidation, inflammatory response, disorders in the metabolism of bile acid, amino acid, fatty acid and lipid, as well as the gut microbiota dysbiosis. Given that gut microbiota is significantly associated with energy expenditure, systemic inflammation and host metabolism, these findings suggest a potential central role of the gut microbiota in mediating the anti-EF effect of WEG. That is, the saccharides and ginsenosides in WEG serve as energy substrates for specific intestinal bacteria, thereby beneficially regulating the gut microbiota, and the reshaped gut microbial ecosystem then triggers several molecular and cellular signaling pathways (e.g. butyrate or TGR5 signals) to achieve the therapeutic effects on EF. The outcomes highlighted here enable deeper insight into how WEG overcomes EF.


Assuntos
Fadiga/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Panax , Esforço Físico , Extratos Vegetais/farmacologia , Aminoácidos/metabolismo , Animais , Bacteroidetes/classificação , Bacteroidetes/crescimento & desenvolvimento , Bacteroidetes/isolamento & purificação , Ácidos e Sais Biliares/metabolismo , Disbiose , Fadiga/etiologia , Ácidos Graxos/metabolismo , Firmicutes/classificação , Firmicutes/crescimento & desenvolvimento , Firmicutes/isolamento & purificação , Metabolismo dos Lipídeos , Masculino , Metaboloma , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-Dawley , Natação
18.
Nat Commun ; 12(1): 2885, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001887

RESUMO

Despite the widespread observations on the osteogenic effects of magnesium ion (Mg2+), the diverse roles of Mg2+ during bone healing have not been systematically dissected. Here, we reveal a previously unknown, biphasic mode of action of Mg2+ in bone repair. During the early inflammation phase, Mg2+ contributes to an upregulated expression of transient receptor potential cation channel member 7 (TRPM7), and a TRPM7-dependent influx of Mg2+ in the monocyte-macrophage lineage, resulting in the cleavage and nuclear accumulation of TRPM7-cleaved kinase fragments (M7CKs). This then triggers the phosphorylation of Histone H3 at serine 10, in a TRPM7-dependent manner at the promoters of inflammatory cytokines, leading to the formation of a pro-osteogenic immune microenvironment. In the later remodeling phase, however, the continued exposure of Mg2+ not only lead to the over-activation of NF-κB signaling in macrophages and increased number of osteoclastic-like cells but also decelerates bone maturation through the suppression of hydroxyapatite precipitation. Thus, the negative effects of Mg2+ on osteogenesis can override the initial pro-osteogenic benefits of Mg2+. Taken together, this study establishes a paradigm shift in the understanding of the diverse and multifaceted roles of Mg2+ in bone healing.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Fêmur/efeitos dos fármacos , Imunomodulação/efeitos dos fármacos , Macrófagos/metabolismo , Magnésio/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Canais de Cátion TRPM/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/imunologia , Citocinas/metabolismo , Fêmur/metabolismo , Fêmur/patologia , Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/metabolismo , Macrófagos/citologia , Macrófagos/imunologia , Magnésio/administração & dosagem , Magnésio/metabolismo , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Proteínas Serina-Treonina Quinases/genética , Ratos Sprague-Dawley , Células THP-1 , Canais de Cátion TRPM/genética
19.
Acta Cir Bras ; 36(3): e360307, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33978063

RESUMO

PURPOSE: To probe the mechanism of mild hypothermia combined with rutin in the treatment of spinal cord injury (SCI). METHODS: Thirty rats were randomized into the following groups: control, sham, model, mild hypothermia (MH), and mild hypothermia plus rutin (MH+Rutin). We used modified Allen's method to injure the spinal cord (T10) in rats, and then treated it with MH or/and rutin immediately. BBB scores were performed on all rats. We used HE staining for observing the injured spinal cord tissue; ELISA for assaying TNF-α, IL-1ß, IL-8, Myeloperoxidase (MPO), and Malondialdehyde (MDA) contents; Dihydroethidium (DHE) for measuring the reactive oxygen species (ROS) content; flow cytometry for detecting apoptosis; and both RT-qPCR and Western blot for determining the expression levels of TGF-ß/Smad pathway related proteins (TGF-ß, Smad2, and Smad3). RESULTS: In comparison with model group, the BBB score of MH increased to a certain extent and MH+Rutin group increased more than MH group (p < 0.05). After treatment with MH and MH+Rutin, the inflammatory infiltration diminished. MH and MH+Rutin tellingly dwindled TNF-ß, MDA and ROS contents (p < 0.01), and minified spinal cord cell apoptosis. MH and MH+Rutin could patently diminished TGF-ß1, Smad2, and Smad3 expression (p < 0.01). CONCLUSIONS: MH+Rutin can suppress the activation of TGF-ß/Smad pathway, hence repressing the cellular inflammatory response after SCI.


Assuntos
Hipotermia , Traumatismos da Medula Espinal , Animais , Ratos , Ratos Sprague-Dawley , Rutina/uso terapêutico , Medula Espinal , Traumatismos da Medula Espinal/terapia , Fator de Crescimento Transformador beta
20.
Wei Sheng Yan Jiu ; 50(2): 267-273, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33985636

RESUMO

OBJECTIVE: To study the effect of calcium content on bone mineral density and intestinal microbiota in ovariectomized rats. METHODS: A total of 30 Wistar rats were randomly divided into 3 groups, namely the sham operation group, the model group and the calcium carbonate supplement group. Postmenopausal osteoporosis rats were established by ovariectomy(OVX). After the first week of modeling, each group was intragastric separately. The calcium carbonate solution was given to the calcium carbonate supplement group, and the same amount of sterile water was given to the other two groups. The animals were executed at the end of the 12 weeks. Left femur was taken and bone mineral density(BMD) was detected by dual-energy X-ray absorptiometry. The total DNA of fecal samples was aseptically extracted and the Illumina Miseq platform was to carry out high-throughput sequencing. RESULTS: Compared with the sham operation group, the body mass increment of rats in the model group was significantly increased, the level of BMD was significantly reduced(P<0. 05), the intestinal microbiota diversity was not significantly changed, the Firmicutes abundance was decreased, and the Bacteroidetes abundance was increased. Compared with the model group, the body mass increment of rats in the calcium carbonate supplementation group was significantly reduced and BMD was significantly increased(P<0. 05). There was no significant change in the intestinal microbiota diversity, Firmicutes were increased, and Bacteroidetes were decreased. CONCLUSION: Calcium supplementation can improve bone mineral density and inhibit the increase of body mass during the experiment period, and its mechanism may be related to regulating the structure of intestinal microbiota.


Assuntos
Microbioma Gastrointestinal , Osteoporose , Animais , Densidade Óssea , Cálcio , Feminino , Humanos , Osteoporose/prevenção & controle , Ovariectomia , Ratos , Ratos Sprague-Dawley , Ratos Wistar
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