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1.
Food Funct ; 9(11): 5891-5902, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30375606

RESUMO

Acetaminophen (APAP) is commonly used to relieve pain and fever in a clinical setting, but its excessive use can lead to serious hepatotoxicity. Our previous study demonstrated that polydatin (PD) can effectively attenuate d-galactose- and alcohol-induced hepatotoxicity, however, its effect on APAP-induced hepatotoxicity is still unknown. In this study, we explore the protective effect and potential mechanism of PD against APAP-induced hepatotoxicity in mice. The results indicate that PD effectively improves the survival of mice with APAP-induced hepatotoxicity, significantly alleviating histopathologic alterations in the liver, and decreasing the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). PD significantly and dose-dependently reduces oxidative stress by lowering the content of oxidized glutathione (GSSG), reactive oxygen species (ROS), nitric oxide (NO) and malonaldehyde (MDA), while enhancing the hepatic activities of glutathione (GSH), glutathione peroxidase (GSH-Px) and the GSH/GSSG ratio. Meanwhile, PD also substantially inhibits the levels and mRNA expressions of inducible nitric oxide synthase (iNOS) and NADPH oxidase 2 (NOX2). Additionally, PD markedly arrests apoptosis by assuaging TUNEL-positive hepatocytes and the apoptotic index, decreasing the levels and expression of cytochrome c (CytC), cleaved-caspase-9, apoptotic protease activating factor 1 (Apaf-1), cleaved-caspase-3, and Bax and increasing the level and expression of Bcl-2. Overall, PD pretreatment shows a potent protective effect against APAP-induced hepatotoxicity by relieving oxidative stress and inhibiting apoptosis.


Assuntos
Acetaminofen/toxicidade , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Glucosídeos/farmacologia , Substâncias Protetoras/farmacologia , Estilbenos/farmacologia , Alanina Transaminase/sangue , Animais , Antioxidantes/metabolismo , Fator Apoptótico 1 Ativador de Proteases/genética , Fator Apoptótico 1 Ativador de Proteases/metabolismo , Aspartato Aminotransferases/sangue , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Glutationa/sangue , Dissulfeto de Glutationa/sangue , Dissulfeto de Glutationa/metabolismo , Glutationa Peroxidase/sangue , Glutationa Peroxidase/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/sangue , Camundongos , Camundongos Endogâmicos ICR , NADPH Oxidase 2/genética , NADPH Oxidase 2/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
2.
Eur J Pharmacol ; 811: 222-231, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28648405

RESUMO

Coptisine is one of the main constituents of Coptis chinensis which has been widely used for the remedy of inflammatory disorders. Although the biological activities of coptisine have been well known, the pharmacological properties of its free base have seldomly been elucidated thus far. The aim of this study was to investigate the potential anti-inflammatory properties of coptisine free base (CFB, 8-hydroxy-7,8-dihydrocoptisine) on three animal models, namely xylene-induced ear edema, acetic acid-induced vascular permeability and carrageenan-induced paw edema. The results exhibited that CFB exerted a dose-dependent suppression on ear edema induced by xylene, significantly mitigated the aggravation of vascular permeability caused by acetic acid and paw edema induced by carrageenan. Additionally, CFB significantly suppressed the productions of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), prostaglandinE2 (PGE2) and tumor necrosis factor (TNF-α) in the drug-treated groups as compared with the vehicle group after treatment with carrageenan. Signaling events of nuclear factor-κB (NF-κB) translocation, such as p-IKKα, p-IKKß, p-IκBα and p65 (nucleus) were significantly inactivated, while inhibitor of nuclear factor κBα (IκBα) and p65 (cytosolic) were markedly up-regulated by CFB. Furthermore, CFB also significantly suppressed the mitogen-activated protein kinase (MAPK) pathway by blocking the phosphorylation of p-p38 (phospho-p38 mitogen-activated protein kinases) and p-JNK (phospho-c-jun N-terminal kinase) but not p-ERK (phospho-extracellular signal-regulated kinase). Hence, CFB efficiently prevented inflammation, at least partially, via inhibition of NF-κB and MAPK pathways. These findings provided a pioneering pharmacological basis for the anti-inflammatory effect of CFB and suggested CFB might be a potential candidate for the therapy of inflammatory disorders.


Assuntos
Anti-Inflamatórios/farmacologia , Berberina/análogos & derivados , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Ácido Acético/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Berberina/farmacologia , Berberina/uso terapêutico , Permeabilidade Capilar/efeitos dos fármacos , Dinoprostona/metabolismo , Relação Dose-Resposta a Droga , Edema/tratamento farmacológico , Edema/metabolismo , Edema/patologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
3.
J Med Food ; 20(2): 180-188, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28146409

RESUMO

Constipation is a common disorder that is a significant source of morbidity among people around the world ranging from 2% to 28%. Dendrobium officinale Kimura et Migo is a traditional herbal medicine and health food used for tonicity of the stomach and promotion of body fluid production in China. This study aimed to prepare the ultrafine powder of Dendrobium officinale (UDO) and investigate its laxative effect and potential mechanism in mice with diphenoxylate-induced constipation. Results indicated that the mean diameter (d50) of UDO obtained by ball milling was 6.56 µm. UDO (62.5, 125, and 250 mg/kg, p.o.) could significantly enhance the gastrointestinal transit ratio and promote fecal output. Moreover, UDO treatment resulted in significant increases in the serum levels of acetylcholinesterase (AChE), gastrin (Gas), motilin (MTL), and substance P (SP), and obviously decreased serum contents of somatostatin (SS). Taken together, UDO, which can be easily obtained through milling to a satisfactory particle size, exhibited obvious laxative effect in diphenoxylate-induced constipated mice, and the mechanism might be associated with elevated levels of AChE, Gas, MTL, SP, and reduced production of SS. UDO has the potential for further development into an alternative effective diet therapy for constipation.


Assuntos
Constipação Intestinal/tratamento farmacológico , Dendrobium/química , Laxantes/administração & dosagem , Extratos Vegetais/administração & dosagem , Animais , Constipação Intestinal/metabolismo , Constipação Intestinal/fisiopatologia , Feminino , Gastrinas/metabolismo , Trânsito Gastrointestinal/efeitos dos fármacos , Humanos , Laxantes/química , Masculino , Camundongos , Camundongos Endogâmicos ICR , Motilina/metabolismo , Extratos Vegetais/química , Substância P/metabolismo
4.
Fa Yi Xue Za Zhi ; 28(4): 247-51, 2012 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-23033660

RESUMO

OBJECTIVE: To investigate the changes of collagen fibers and the expression of osteopontin in the left ventricle in cases of hypertrophic cardiomyopathy (HCM), along with the significance of their potential forensic application. METHODS: Fifteen cases of HCM, 15 cases of coronary heart disease with cardiac hypertrophy and 20 cases of traffic accidents were selected as HCM group, coronary heart disease group and control group, respectively. Collagen volume fraction and osteopontin expression were observed and compared by HE staining, Masson trichrome staining and immunohistochemistry methods. Imaging and statistical methods were used for quantitative analysis. RESULTS: Collagen volume fraction in left ventricle of HCM and coronary heart disease were significantly higher than that in the control group (P < 0.05), which was not significantly different between the HCM group and the coronary heart disease group. The integral light density value of osteopontin in left ventricular cardiomyocytes of the HCM group and the coronary heart disease group were significantly higher than that of the control group (P< 0.05), and the value of the HCM group was also significantly higher than that of coronary heart disease group (P < 0.05). CONCLUSION: The increased contents of collagen fibers and the overexpression of osteopontin may play an important role in myocardial fibrosis, and they can be used as markers in aid of diagnosing sudden death due to HCM.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico , Doença das Coronárias/diagnóstico , Ventrículos do Coração/patologia , Miocárdio/patologia , Osteopontina/metabolismo , Cardiomiopatia Hipertrófica/metabolismo , Cardiomiopatia Hipertrófica/fisiopatologia , Estudos de Casos e Controles , Colágeno/metabolismo , Doença das Coronárias/metabolismo , Doença das Coronárias/fisiopatologia , Morte Súbita Cardíaca/etiologia , Feminino , Fibrose , Patologia Legal , Humanos , Imuno-Histoquímica , Masculino , Miocárdio/metabolismo , Coloração e Rotulagem
5.
Shock ; 36(3): 289-94, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21558980

RESUMO

Many studies have examined the association between coffee consumption and risk of cardiovascular disease, but the results remain controversial. Caffeine is one of the main biologically active compounds of coffee. The aim of this study was to investigate the potential role of caffeine on myocardial ischemia/reperfusion (I/R) injury in the rats. We administered caffeine (25 mg/kg per day) or saline in rats for 4 weeks before myocardial ischemia/reperfusion operation. Compared with the sham group, caffeine treatment decreased ischemia-associated infarct size, serum creatine kinase, and lactate dehydrogenase 3-h reperfusion after 30-min ischemia. Myocardial neutrophil infiltration (assessed by myeloperoxidase activity) was significantly decreased compared with the control group. Meanwhile, caffeine reduced the myocardial apoptosis and suppressed the activation of caspase 3 during myocardial I/R. Importantly, we observed a strong poly(ADP-ribose) polymerase (PARP) activation during myocardial I/R, and caffeine administration inhibited PARP activation and attenuated the expression of PARP-related proinflammatory mediators such as inducible nitric oxide synthetase, IL-6, and TNF-α, all of which may be correlated with downregulated nuclear factor κB activity. We concluded that caffeine protected against myocardial I/R injury by inhibiting inflammation and apoptosis.


Assuntos
Cafeína/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Caspase 3/metabolismo , Creatina Quinase/sangue , Ensaio de Desvio de Mobilidade Eletroforética , Hidroliases/sangue , Imuno-Histoquímica , Interleucina-6/sangue , Masculino , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/imunologia , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/sangue
6.
J Cell Biochem ; 112(7): 1787-94, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21381076

RESUMO

Cardiac hypertrophy, a major determinant of heart failure, is associated with heat shock proteins (HSPs). HSP75 has been reported to protect against environmental stresses; however, its roles in cardiac hypertrophy remain unclear. Here, we generated cardiac-specific inducible HSP75 transgenic mice (TG) and cardiac hypertrophy was developed at 4 weeks after aortic banding in TG mice and wild-type littermates. The results revealed that overexpression of HSP75 prevented cardiac hypertrophy and fibrosis as assessed by heart weight/body weight ratio, heart weight/tibia length ratio, echocardiographic and hemodynamic parameters, cardiomyocyte width, left ventricular collagen volume, and gene expression of hypertrophic markers. Further studies showed that overexpression of HSP75 inhibited the activation of TAK/P38, JNK, and AKT signaling pathways. Thus, HSP75 likely reduces the hypertrophy and fibrosis induced by pressure overload through blocking TAK/P38, JNK, and AKT signaling pathways.


Assuntos
Cardiomegalia/genética , Proteínas de Choque Térmico HSP90/genética , Miocárdio/patologia , Proteínas Recombinantes/genética , Animais , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/metabolismo , Peso Corporal , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Tamanho Celular , Colágeno/metabolismo , Fibrose , Proteínas de Choque Térmico HSP90/metabolismo , Ventrículos do Coração/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Células Musculares/metabolismo , Células Musculares/patologia , Miocárdio/metabolismo , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Tamanho do Órgão , Fosforilação , Proteínas Recombinantes/metabolismo , Transcrição Genética , Pressão Ventricular , Remodelação Ventricular
7.
Zhonghua Xin Xue Guan Bing Za Zhi ; 38(4): 369-73, 2010 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-20654087

RESUMO

OBJECTIVE: To investigate the effects of curcumin on sarcoplasmic reticulum Ca2+-ATPase in heart failure rabbits. METHODS: Rabbit heart failure model was made with aortic regurgitation and abdominal aorta constriction and 40 rabbits were randomly divided into 4 groups including: (1) heart failure treated with curcumin; (2) heart failure treated with placebo; (3) healthy control treated with curcumin and (4) healthy control treated with placebo. All rabbits were administrated with curcumin capsules or placebo capsules 100 mg x kg(-1) x d(-1), respectively. All groups were sacrificed after eight weeks. Myocardial ultrastructural organization was detected by transmission electron microscope. RT-PCR and Western blot were used to measure the expression of sarcoplasmic reticulum Ca2+-ATPase in mRNA and protein levels, respectively. Malachite green colorimetric assay was used to evaluate the activity of sarcoplasmic reticulum Ca2+-ATPase. RESULTS: All detected parameters were similar between control curcumin group and control placebo group. Compared with the control groups (Groups 3 and 4), the heart/body weight ratio was significantly increased in the heart failure-curcumin group (Group 1) and the heart failure-placebo group (Group 2, all P < 0.05), but the ratio was significantly lower in heart failure-curcumin group than in heart failure-placebo group (P < 0.05). The degree of heart failure was decreased by curcumin. Activity and mRNA and protein expression for sarcoplasmic reticulum Ca2+-ATPase were significantly reduced in the heart failure-placebo group and which could be significantly attenuated by curcumin (all P < 0.05). CONCLUSION: Curcumin could improve cardiac function via upregulating the expression of sarcoplasmic reticulum Ca2+-ATPase in this model.


Assuntos
Curcumina/farmacologia , Insuficiência Cardíaca/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Retículo Sarcoplasmático/efeitos dos fármacos , Retículo Sarcoplasmático/metabolismo , Animais , Cálcio/metabolismo , RNA Mensageiro/genética , Coelhos
8.
Zhonghua Xin Xue Guan Bing Za Zhi ; 38(3): 225-9, 2010 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-20450564

RESUMO

OBJECTIVE: To investigate the influences of verapamil preconditioning on cardiac function in vitro and intracellular free Ca2+ and L-type calcium current (I(Ca-L)) in rat cardiomyocytes post ischemia-reperfusion (I/R) injury. METHODS: The isolated rat hearts in control group (37 degrees C Tyrode solution perfusion for 30 min, n = 6), I/R group (no flow for 30 min followed 30 min reperfusion with 37 degrees C Tyrode solution, n = 7) and verapamil preconditioning group [37 degrees C Tyrode solution perfusion for 10 min, adding verapamil (20 micromol/L) to Tyrode solution and perfusion for another 30 min, followed then by 30 min no flow and 30 min reperfusion, n = 7] using Langendorff perfusion system. The fluorescence intensity of intracellular Ca2+ was detected with Fluo-3/AM loading by the laser scanning confocal microscope. The I(Ca-L) was recorded via whole-cell patch clamp technique in enzymatically dissociated single rat ventricular myocytes. RESULTS: As expected, arrhythmias and cardiac dysfunction were shown post I/R injury. The fluorescence intensities of intracellular free Ca2+ in cardiomyocytes were significantly increased compared with control group (P < 0.01). By voltage clamp protocol, peak current densities of I(Ca-L) was significantly reduced and I-V curve significantly elevated. Post I/R injury compared with control group (P < 0.01) which could be reversed by Verapamil preconditioning. Verapamil preconditioning also significantly improved diastolic and systolic functions, and reduced the incidence of arrhythmias. CONCLUSIONS: Myocardial I/R injury might significantly impair heart functions and induce arrhythmias via cellular Ca2+ overload. Verapamil preconditioning could prevent heart I/R injury and reduce arrhythmias by decreasing influx of I(Ca-L), thereby stabilizing cardiomyocytes in myocardial stunning and avoiding occurrence of Ca2+-induced Ca2+ release during I/R injury.


Assuntos
Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Verapamil/farmacologia , Animais , Cálcio/metabolismo , Canais de Cálcio Tipo L/efeitos dos fármacos , Precondicionamento Isquêmico Miocárdico/métodos , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Ratos , Ratos Sprague-Dawley
9.
Zhonghua Yi Xue Za Zhi ; 90(42): 3003-7, 2010 Nov 16.
Artigo em Chinês | MEDLINE | ID: mdl-21211315

RESUMO

OBJECTIVE: To investigate the effects and mechanism of verapamil preventing ischemia/reperfusion (I/R) injury by cardiac performance intracellular free [Ca(2+)](i) and L-type calcium current (I(Ca-L)) in cardiomyocytes of diabetes mellitus rats. METHODS: Diabetic rats were streptozotocin-induced and received verapamil (8 mg×kg(-1)×d(-1)) from 6 - 14 weeks old. The in vitro heart models of I/R rats were randomly divided into normal control group diabetes group, verapamil control group. the changes of heart functions were observed through a Langendorff-perfusion system. The fluorescence intensity of intracellular Ca(2+) was detected with Fluo-3/AM loading by laser scanning confocal microscope. I(Ca-L) was recorded by the whole-cell technique of patch clamp in enzymatically dissociated single rat ventricular myocytes. RESULTS: (1) In verapamil diabetes group, the values of left ventricular developed pressure [(91.3 ± 4.6) mm Hg], diastolic end pressure [(1535 ± 280) mm Hg], the maximum rising rates of left ventricular pressure [(5833 ± 256) mm Hg/s] and coronary arterial flow [(13.7 ± 0.9) ml/min] were all significantly increased, and the maximum dropping rates of left ventricular pressure [(3504 ± 319) mm Hg/s] was obviously decreased (compared with diabetes group, P < 0.01, respectively). (2) The fluorescence intensities of intracellular free Ca(2+)[(155.6 ± 10.9) nmol/L] in verapamil diabetes group were significantly reduced compared with diabetes group (245.2 ± 17.5 nmol/L, P < 0.01). (3) When clamp voltage was -20mV, I(Ca-L) was (-6.81 ± 0.76) pA/pF in verapamil diabetes group (compared with normal group (-8.17 ± 2.07) pA/pF, P < 0.05, and with diabetes group (-3.21 ± 0.54) pA/pF, P < 0.01, and with verapamil control group (-7.14 ± 2.17) pA/pF, P > 0.05). The current-voltage curve was changed to the lower position with -20mV of peak clamp potential in verapamil diabetes group compared with diabetes group. CONCLUSION: A poor heart function is closely correlated with a rising [Ca(2+)]i and a declining I(Ca-L) associated with I/R injury in diabetic rats hearts. Along-term verapamil therapy may significantly improve the severe cardiac impairment. The mechanism is probably attributed to the fact that verapamil can adjust I(Ca-L) influx, normalize the balance of intercellular [Ca(2+)]i, and block the Ca(2+) overload trigger by the effects of Ca(2+)-induced Ca(2+) release in diabetic cardiomyocytes.


Assuntos
Diabetes Mellitus Experimental , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Verapamil/farmacologia , Animais , Cálcio/metabolismo , Canais de Cálcio Tipo L/metabolismo , Diabetes Mellitus Experimental/metabolismo , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Ratos , Ratos Sprague-Dawley
10.
Zhonghua Xin Xue Guan Bing Za Zhi ; 36(4): 355-9, 2008 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-19100017

RESUMO

OBJECTIVE: To investigate the role of heterogeneous expression of calcium handling proteins and spatial heterogeneity of APD restitution in the maintenance mechanism of ventricular fibrillation. METHODS: During programmed electrical simulation, APD restitution curves in the endocardium and epicardium of LV were constructed by plotting APD100 and diastolic interval. APD alternans, delayed after depolarization events were recorded simultaneously. Endocardial and epicardial myocytes were isolated from LV base and apex. Real time-PCR and Western blotting were performed to determine the relative messenger RNA and protein expression levels of calcium handling proteins. RESULTS: The normal hearts have spatial heterogeneity of action potential restitution property and transmural heterogeneity of calcium handling proteins. The slopes of the APD restitution curve in the endocardium were significantly steeper than those in epicardium, and the slopes of APD curve at the LV apex were significantly steeper than those in LV base. However, delayed after depolarization events with larger amplitude and earlier onset consistently occurred in the endocardium of LV base. After programmed electrical simulation, the expression of messenger RNA of RyR2, SERCA2a except for Calstabin2 significantly decreased (by 57% and 41%, respectively, P < 0.05) in the endocardium of the base, while the expression of RyR2, SERCA2a, Calstabin2 significantly increased (by 90%, 78%and 64%, respectively, P < 0.05) in the epicardium of LV base. Although transmural heterogeneity of calcium handling proteins at the LV apex were also observed after rapid pacing, there is no significant differences in the transmural heterogeneity at the LV apex compared to the LV base. The base of LV has unique calcium handling properties. CONCLUSIONS: It has been shown that Calcium cycling could modulate APD restitution property in the intact heart. The interaction between action potential and calcium dynamics instabilities is one of the most important reasons why simple criterion such as the APD restitution slope > 1 may fail to accurately predict the onset of APD alternans.


Assuntos
Calmodulina/metabolismo , Fibrilação Ventricular/metabolismo , Fibrilação Ventricular/fisiopatologia , Potenciais de Ação , Animais , Cálcio/metabolismo , Masculino , Suínos
11.
Inflammation ; 30(3-4): 97-104, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17497204

RESUMO

The aim of the present study was to investigate the role of anti-inflammation for MSCs transplantation in rat models of myocardial infarction. Rats with AMI induced by occlusion of the left coronary artery were randomized to MSCs transplantation group, MI group and sham operated group. The effects of MSCs transplantation on cardiac inflammation and left ventricular remodeling in non-infarcted zone were observed after 4 weeks of MI. We found that MSC transplantation (1) decreased protein production and gene expression of inflammation cytokines TNF-alpha, IL-1beta and IL-6, (2) inhibited deposition of type I and III collagen, as well as gene and protein expression of MMP-1 and TIMP-1, (3) attenuated LV cavitary dilation and transmural infarct thinning, thus prevent myocardial remodeling after myocardial infarction, and (4) increased EF, FS, LVESP and dp/dtmax (P < 0.01), decreased LVDd, LVEDV, LVEDP (P < 0.05). Anti-inflammation role for MSCs transplantation might partly account for the cardiac protective effect in ischemic heart disease.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Infarto do Miocárdio/imunologia , Infarto do Miocárdio/terapia , Animais , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Ecocardiografia , Expressão Gênica/imunologia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/imunologia , Hipertrofia Ventricular Esquerda/terapia , Interleucina-1beta/genética , Interleucina-6/genética , Masculino , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Infarto do Miocárdio/diagnóstico por imagem , Miocardite/diagnóstico por imagem , Miocardite/imunologia , Miocardite/terapia , Miocárdio/metabolismo , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator de Necrose Tumoral alfa/genética
12.
Life Sci ; 80(19): 1746-53, 2007 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-17382969

RESUMO

The hyperpolarization-activated, cyclic nucleotide-gated cation channels (HCN) have been identified as a key factor of cardiac pacemaker activity. The present study investigated the feasibility of using transfection of HCN4, an important subunit in the HCN family, to cure an experimental cardiac bradyarrhythmia. Two adenoviral vectors containing HCN4 and GFP (Ad-HCN4) or GFP alone (Ad-GFP) were constructed. Three or four days after gene injection, the pigs underwent catheter ablation of the atrioventricular (AV) node. After a complete AV block was created, the idioventricular heart rate in the Ad-HCN4 group was significantly greater than in controls. The heart rhythm in the Ad-HCN4 group could be modulated by the beta-adrenergic agonist isoproterenol. An I(f) current could be observed in the ventricular myocytes of the Ad-HCN4 group under patch clamp technique investigations. The expected cell membrane localization of GFP-tagged HCN4 expression was confirmed with confocal fluorescent microscopy. The successful in vivo transfection with Ad-HCN4 was also identified by real-time reverse transcription polymerase chain reaction (RT-PCR). Our study suggested that site-specific gene therapy for cardiac bradyarrhythmias using adenoviral vectors to overexpress HCN4 channels might be feasible.


Assuntos
Terapia Genética/métodos , Bloqueio Cardíaco/terapia , Canais Iônicos/genética , Proteínas Musculares/genética , Adenoviridae/genética , Agonistas Adrenérgicos beta/farmacologia , Animais , Membrana Celular/química , Canais de Cátion Regulados por Nucleotídeos Cíclicos , Vetores Genéticos/genética , Proteínas de Fluorescência Verde/análise , Proteínas de Fluorescência Verde/genética , Frequência Cardíaca/efeitos dos fármacos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização , Canais Iônicos/análise , Isoproterenol/farmacologia , Microscopia Confocal , Proteínas Musculares/análise , Canais de Potássio , RNA Mensageiro/análise , Sus scrofa , Transfecção
13.
Acta Pharmacol Sin ; 25(7): 876-86, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15210060

RESUMO

AIM: To investigate whether autologous transplantation of adult stem cells could improve post-infarcted heart function. METHODS: Bone marrow mononuclear cells (MNCs) were isolated from adult rabbits' tibias after coronary ligation. These cells were exposed to 5-azacytidine 10 micromol/L for 24 h on the third day of culture. After being labeled with bromodeoxyuridine (BrdU), the cells were auto-transplanted into bordering zone of the infarcted area at 2 weeks after injury. The animals were killed at 3 days, 2 weeks, 1 month, and 2 months after transplantation, respectively. The left ventricular functions, capillary density, and cardiac nerve density were measured and the differentiation of the engrafted cells was determined by immunostaining. RESULTS: BrdU-labeled MNCs were well aligned with the host cardiomyocytes. Parts of them were incorporated into capillary and arteriolar vessel walls. In addition to inducing angiogenic ligands (basic fibroblast growth factor, vascular endothelial growth factor) and inflammation cytokines (interleukin 1-beta) during the early period of MNCs implantation, MNCs induced 2.0-fold increase in capillary density as well. Moreover, GAP43-positive and TH-positive nerve density were markedly higher in the MNCs-treated groups than that in the non-treated hearts. Left ventricular ejection fraction, LV+dp/dt(max), and LV-dp/dt(max) were 47%, 67%, and 55% in MNCs-treated heart respectively, which was higher than that of the control heart, whereas left ventricular end-diastolic volume, left ventricular end-diastolic diameter, and left ventricular end-diastolic pressure were 45%, 22%, and 50% respectively in MNCs-treated heart, which was lower than that of the control heart at 2 months after cell transplantation. CONCLUSION: Autologous transplantation of MNCs induced angiogenesis and nerve sprouting and improved left ventricular diastolic function.


Assuntos
Transplante de Medula Óssea , Coração/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Função Ventricular Esquerda , Animais , Células da Medula Óssea , Células Cultivadas , Fatores de Crescimento Endotelial/sangue , Fator 2 de Crescimento de Fibroblastos/sangue , Proteína GAP-43/metabolismo , Coração/inervação , Interleucina-1/sangue , Infarto do Miocárdio/cirurgia , Neovascularização Fisiológica , Coelhos , Transplante Autólogo , Tirosina 3-Mono-Oxigenase/metabolismo
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