RESUMO
OBJECTIVE: To explore the pathogenesis of male sexual dysfunction by studying cell apoptosis and carbonate monoxide (CO) contents in the penile tissue of rats at different ages. METHODS: We equally divided 24 male Wistar rats into an adult group (8 months old), an elderly group (16 months old) and an aged group (24 months old), and detected cell apoptosis by HE staining and TUNEL and CO levels in the penile tissues of different groups by modified dual-wavelength spectrophotometry. RESULTS: Cell apoptosis increased with aging: 4.38 +/- 1.06 in the adult, 9.38 +/- 1.69 in the elderly and 18.50 +/- 1.60 in the aged group, while the CO content decreased with aging: 12.19 +/- 0.87 in the adult, 7.93 +/- 0.63 in the elderly and 5.68 +/- 0.62 in the aged group, both with statistically significant differences among the 3 groups (P < 0.05). The change of cell apoptosis showed a good negative correlation with that of the CO content (r = -0.889, P < 0.01). CONCLUSION: Cell apoptosis and CO content change in the penile tissue of aging rats, and CO may participate in the development of ED by regulating cell apoptosis.
Assuntos
Envelhecimento , Apoptose , Monóxido de Carbono/metabolismo , Pênis/citologia , Pênis/metabolismo , Animais , Masculino , Ratos , Ratos WistarRESUMO
OBJECTIVE: To study the changes in the activities of carbon monoxide (CO) and heme oxygenase 2 (HO-2) in ED rats with hyperhomocysteinemia (HHcy). METHODS: This study included 40 male Wistar rats weighing 280 - 310 g, 10 as normal controls (group A). HHcy models were made in the other 30 by giving 3% methionine for 4 weeks, and then divided into groups B, C and D. The rats in group B continued to be fed with 3% methionine, those in group C were treated with betaine hydrochloride, and those in group D were given zinc porphyrin IX at 45 micromol per kg per d. Penile erections of the rats were recorded, and 4 weeks later, all were killed for determination of the levels of homocysteine (Hcy) in the blood plasma and the activities of CO and HO-2 in the corpus cavernosum of the penis. RESULTS: The level of plasma Hcy, penile erection frequency and the content of CO in the corpus cavernosum were (12.55 +/- 0.82) micromol/L, (1.88 +/- 0.05) times and (10.55 +/- 1.73) micromol/L in group A, the Hcy level significantly higher while the penile erection frequency and CO content remarkably lower than in group B ([25.01 +/- 0.94] micromol/L, [0.70 +/- 0.05] times and [9.51 +/- 1.52] micromol/L, P < 0.05 or P < 0.01), with a negative correlation between the level of Hcy and that of CO and HO-2 (P < 0.01). Compared with group B, the three parameters were all significantly increased in C ([14.37 +/- 0.47] micromol/L, [1.18 +/- 0.08] times and [10.36 +/- 1.56] micromol/L, all P < 0.05 or P < 0.01). CONCLUSION: Decreased expressions of CO and HO-2 in the corpus cavernosum of the penis may result in ED in HHcy rats. Betaine can reduce the Hcy level in the blood plasma and CO content in the corpus cavernosum, which might be one of the mechanisms of its action on ED with HHcy.
Assuntos
Disfunção Erétil/sangue , Heme Oxigenase (Desciclizante)/sangue , Homocisteína/sangue , Hiper-Homocisteinemia/metabolismo , Pênis/metabolismo , Animais , Monóxido de Carbono/sangue , Disfunção Erétil/metabolismo , Hiper-Homocisteinemia/sangue , Masculino , Ratos , Ratos WistarRESUMO
OBJECTIVE: To study the correlation of homocysteine (Hcy) in plasma with nitric oxide synthetase (NOS) and endogenous carbon monoxide (CO) in the penile corpus cavernosum of type 2 diabetic rats. METHODS: This study included 40 male Wistar rats, 10 as controls (Group A) and the other 30 as diabetes mellitus (DM) models. Four weeks after the model establishment, the model rats were divided into a DM group (Group B, n = 10), an insulin treated group (Group C, n = 10), and a folic acid and vitamin B12 treated group (Group D, n = 10). All the rats were injected with apomorphine and observed for penile erection at 8 and 12 weeks, and the levels of total plasma Hcy (tHcy), NOS and CO in the penile corpus cavernosum were measured at 12 weeks. RESULTS: Compared with Group A, the level of tHcy was significantly increased, while NOS and CO activities in the penile cavernous tis-sue and erectile function remarkably decreased in Group B (P < 0.01). The incidence rate of high Hcy was 55% in the DM rats. In comparison, the level of tHcy was obviously decreased, and the NOS activity and erectile function markedly increased in Groups C and D (P < 0.01). The Hcy level showed a significant negative correlation with NOS activity (rA = -0.89, rB = -0.76, rc = -0.91, rD = -0.91) and CO content (TA = -0.82, r, = -0.77, rc = -0.93, rD = -0.81). CONCLUSION: High plasma Hcy can decrease NOS and CO activities in the penile corpus cavernosum, and consequently induce erectile dysfunction in DM rats, while insulin, folic acid and vitamin B12 can improve their penile erectile function by increasing NOS and CO activities.
Assuntos
Monóxido de Carbono/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 2/sangue , Homocisteína/sangue , Óxido Nítrico Sintase/metabolismo , Pênis/metabolismo , Animais , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Ácido Fólico/farmacologia , Insulina/farmacologia , Masculino , Pênis/efeitos dos fármacos , Ratos , Ratos Wistar , Vitamina B 12/farmacologiaRESUMO
Background: Bladder cancer is a common urinary system tumor. In the treatment of clinical patients, it is particularly important to find an effective treatment method to inhibit tumor growth. The world's first PARP inhibitor olaparib is mainly used for the treatment of BRCA1/BRCA2 mutated tumors. Metformin, an antidiabetic drug, has been reported to reduce cancer incidence in humans and improve survival in cancer patients. Methods: Cell viability and proliferation were detected by CCK-8 assay and colony formation assay; cell apoptosis was detected by flow cytometry; cell migration and invasion abilities were detected by scratch assay and Transwell assay; STAT3/C-MYC signaling pathway protein were detected by western blotting. Results: Olaparib combined with metformin has better effects on the proliferation, clone formation, migration, invasion, and apoptosis of bladder cancer cells than single drug, indicating that metformin can enhance the inhibitory effect of olaparib on tumor growth and regulate the expression of STAT3/C-MYC signaling pathway proteins. Conclusion: The results of this study showed that metformin could significantly enhance the antitumor effect of olaparib on bladder cancer cells, and these effects were mediated by downregulating STAT3/C-MYC signaling pathway proteins. This finding may have potential clinical application in the treatment of bladder cancer.
Assuntos
Metformina , Neoplasias da Bexiga Urinária , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Metformina/farmacologia , Metformina/uso terapêutico , Ftalazinas , Piperazinas , Proteínas Proto-Oncogênicas c-myc , Transdução de Sinais , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologiaRESUMO
Ganoderma lucidum polysaccharides (GLP) have renal protection effect but there was no study on the diabetic nephropathy. This study was designed to investigate its effect and mechanism using a diabetic rat model induced by streptozotocin (50 mg/kg, i.p.). The diabetic rats were treated with GLP (300 mg/kg/day) for 10 weeks. The blood glucose, glycated hemoglobin, body weight, and the levels of blood creatinine, urea nitrogen, and urine protein were assessed. And renal pathologies were assessed by the tissue sections stained with hematoxylin-eosin, Masson's trichome, and periodic acid-Schiff. The expression of phosphorylated phosphoinositide 3 kinase (p-PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR), the autophagy proteins beclin-1, LC3-II, LC3-I, and P62; the apoptosis-related proteins caspase-3 and caspase-9; and the inflammation markers IL-6, IL-1ß, and TNF-É were assessed. Results showed that GLP alleviated the impairment of renal function by reducing urinary protein excretion and the blood creatinine level and ameliorated diabetic nephropathy. The expression of p-PI3K, p-Akt, and p-mTOR in the diabetic kidney were significantly reduced in the GLP treatment group compared to the without treatment group. GLP treatment activated the autophagy indicators of beclin-1 and the ratio of LC3-II/LC3-I but reduced p62 and also inhibited the expression of caspase-3, caspase-9 and IL-6, IL-1ß, and TNF-É. In conclusion, the effect of GLP amelioration diabetic nephropathy may be via the PI3k/Akt/mTOR signaling pathway by inhibition of the apoptosis and inflammation and activation of the autophagy process.
Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Polissacarídeos/farmacologia , Reishi , Animais , Biomarcadores/metabolismo , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental , Masculino , Ratos , Transdução de Sinais , EstreptozocinaRESUMO
Radix Lithosperm eyrthrorhizon is a common prescription compound in traditional Chinese medicine. Shikonin is a major component of Radix Lithospermi and has various biological activities. We have investigated the inhibitory effect of shikonin on the growth of adenovirus type 3 (AdV3) in vitro. The antiviral function of shikonin against AdV3 and its virus inhibition ratio were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method (MTT). The expression of hexon protein in AdV3 was determined by immunofluorescence assay using laser scanning confocal microscopy (LSCM) and Western blot analysis. In addition, the rate of apoptosis in cells infected by AdV3 was determined by flow cytometry. Shikonin (0.0156-1 µM) inhibited growth of AdV3 in a concentration-dependent manner with a virus inhibition rate of 23.8-69.1%. Expression of hexon protein in AdV3 was higher in the virus control group than in the shikonin-treated groups as determined by immunofluorescence assay and Western blotting (p<0.05). The rate of shikonin-treated HeLa cell apoptosis had a statistically significant decrease with increasing concentration of drug (p<0.05). Our data demonstrate that shikonin possesses anti-AdV3 capabilities and that the potential antiviral mechanism might involve inhibiting the degree of apoptosis and hexon protein expression of AdV.
Assuntos
Infecções por Adenoviridae/tratamento farmacológico , Adenoviridae/efeitos dos fármacos , Antivirais/farmacologia , Proteínas do Capsídeo/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Lithospermum/química , Naftoquinonas/farmacologia , Adenoviridae/crescimento & desenvolvimento , Antivirais/uso terapêutico , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/uso terapêutico , Células HeLa , Humanos , Naftoquinonas/uso terapêutico , Fitoterapia , Raízes de PlantasRESUMO
Hypertension, as one of the major risk factors for cardiovascular disease, significantly affects human health. Prostaglandin E2 (PGE2) and the E3-class prostanoid (EP3) receptor have previously been demonstrated to modulate blood pressure and hemodynamics in various animal models of hypertension. The PGE2-evoked pressor and biochemical responses can be blocked with the EP3 receptor antagonist, L-798106 (N-[(5-bromo-2methoxyphenyl)sulfonyl]-3-[2-(2-naphthalenylmethyl) phenyl]-2-propenamide). In the hypothalamic paraventricular nucleus (PVN), sympathetic excitation can be introduced by PGE2, which can activate EP3 receptors located in the PVN. In such a case, the central knockdown of EP3 receptor can be considered as a potential therapeutic modality for hypertension management. The present study examined the efficacy of the PVN infusion of L-798106, by performing experiments on spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKYs). The rats were administered with chronic bilateral PVN infusion of L-798106 (10 µg/day) or the vehicle for 28 days. The results indicated that the SHRs had a higher mean arterial pressure (MAP), an increased Fra-like (Fra-LI) activity in the PVN, as well as a higher expression of gp91phox, mitogen-activated protein kinase (MAPK), and proinflammatory cytokines in the PVN compared with the WKYs. Additionally, the expression of Cu/Zn-SOD in the PVN of the SHRs was reduced compared with the WKYs. The bilateral PVN infusion of L-798106 significantly reduced MAP, as well as plasma norepinephrine (NE) levels in the SHRs. It also inhibited Fra-LI activity and reduced the expression of gp91phox, proinflammatory cytokines, and MAPK, whereas it increased the expression of Cu/Zn-SOD in the PVN of SHRs. In addition, L-798106 restored the balance of the neurotransmitters in the PVN. On the whole, the findings of the present study demonstrate that the PVN blockade of EP3 receptor can ameliorate hypertension and cardiac hypertrophy partially by attenuating ROS and proinflammatory cytokines, and modulating neurotransmitters in the PVN.
Assuntos
Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/prevenção & controle , Mediadores da Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Antagonistas de Prostaglandina/farmacologia , Receptores de Prostaglandina E Subtipo EP3/antagonistas & inibidores , Sulfonamidas/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Cardiomegalia/metabolismo , Cardiomegalia/fisiopatologia , Cardiomegalia/prevenção & controle , Modelos Animais de Doenças , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Núcleo Hipotalâmico Paraventricular/metabolismo , Núcleo Hipotalâmico Paraventricular/fisiopatologia , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Espécies Reativas de Oxigênio/metabolismo , Receptores de Prostaglandina E Subtipo EP3/metabolismo , Transdução de SinaisRESUMO
OBJECTIVE: To explore the relationship of aging with the changes of endogenous carbon monoxide (CO), cGMP and cAMP contents in the penile tissues of rats. METHODS: Twenty-four male rats were equally divided into an 8-month, a 16-month and a 24-month group, and their penile erection was detected by injecting apomorphine, their penile cavernous body harvested, and the contents of CO, cAPM and cGMP detected by improved dual wavelength spectrophotometry. RESULTS: The contents of CO, cAPM and cGMP were reduced with the increase of age, with statistically significant differences between the three age groups (P < 0.01). CONCLUSION: Aging significantly decreased the contents of CO, cAMP and cGMP in the penile tissues of the rats, which suggests that aging might play an important role in erectile dysfunction.
Assuntos
Envelhecimento/fisiologia , Monóxido de Carbono/metabolismo , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Pênis/metabolismo , Animais , Masculino , Ratos , Ratos WistarRESUMO
OBJECTIVE: To investigate the changes of xanthine oxidase (XOD), myeloperoxidase (MPO) and mitochondrial succinate dehydrogenase (SDH) in the testis and the protective effect of ganoderma lucidum spores on the testicular tissue of rats with non-insu- lin-dependent diabetes mellitus (NIDDM). METHODS: Fifty male Wistar rats were divided randomly into a model, a ganoderma and a normal control group, the first two groups injected with 2% STZ (25 mg/kg) through the peritoneum, and the last one with half-and-half sodium citrate/citrate buffer solution. Two weeks after normal diet, glucose tolerance tests were performed and the rats with abnormal glucose tolerance in the model and ganoderma groups received high-fat and high-carbohydrate food, the latter given ganoderma lycium spores (250 mg/kg x d) in addition, both for 10 weeks and all rats fed alone. Glucose tolerance tests were repeated 1 day before the end of the experiment and the testes of the rats were harvested for the determination of XOD, MPO and SDH. RESULTS: SDH was significantly lower (P < 0.05) while XOD and MPO significantly higher in the model group than in the ganoderma and control groups (P < 0.05). The model rats exhibited abnormal convoluted seminiferous tubules, indistinct parietal layers, decreased or abolished gonepoiesis, luminal peripheral fibrous tissue (interstitial substance) accrementition, basal lamina thickening, and vessel wall fibrous tissue accrementition and sclerosis. CONCLUSION: Ganoderma lucidum spores can protect the testis of diabetic rats by reducing free radical-induced damage to the testicular tissue and enhancing the activity of SDH.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Reishi , Testículo/metabolismo , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Peroxidase/metabolismo , Ratos , Ratos Wistar , Esporos Fúngicos , Succinato Desidrogenase/metabolismo , Xantina Oxidase/metabolismoRESUMO
OBJECTIVE: To observe the effects of ganoderma lucidum spores (GLS) on mitochondrial calcium ion and cytochrome C in the epididymal cells of type 2 diabetes rats. METHODS: Fifty adolescent rats were randomly divided into a model group (n=20), a GLS group (n=20) and a control group (n=10). The animals of the former two groups were injected with 2% STZ via vena caudalis for one time to induce type 2 diabetes. Then the model group was given high-fat-sugar diet, the GLS group high-fat-sugar diet + GLS (250 mg/kg x d), and the control group normal diet + CA-citrate sodium buffer. The bilateral epididymides were obtained 10 weeks later and the contents of mitochondrial calcium and cytochrome C detected. RESULTS: Type 2 diabetes models were successfully constructed. The content of mitochondrial calcium in the epididymal cells was significantly higher in the model group ([3.279 +/- 0.502] mg/L) than in the control group ([2.606 +/- 0.048] mg/L, P < 0.01), with no significant difference between the GLS group ([2.693 +/- 0. 196] mg/L) and the control (P > 0.05). In the model group, the content of mitochondrial cytochrome C ([3.213 +/- 1.511] micromol/L) was significantly lower (P < 0.05) while that of cytoplasm cytochrome C ([2.484 +/- 0.661] micromol/L) significantly higher (P < 0.05) than in the control ([5.688 +/- 1.679] micromol/L and [1.574 +/- 0.329] micromol/L, respectively). In the GLS group, the content of mitochondrial cytochrome C ([5.258 +/- 1.560] micromol/L) was higher, with no significant difference (P > 0.05), and that of cytoplasm cytochrome C ([1.727 +/- 0.396] micromol/L) significantly lower than in the model group (P < 0.05), but the difference between the GLS and the control group was not significant (P > 0.05). CONCLUSION: With disequilibrium of calcium homeostasis and damage to mitochondria, there might be excessive apoptosis in the epididymal cells of type 2 diabetes rats. Ganoderma lucidum spores could protect epididymal cells and counteract their apoptosis in diabetic condition.
Assuntos
Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 2/terapia , Reishi , Esporos Fúngicos , Animais , Cálcio/metabolismo , Citocromos c/metabolismo , Epididimo/citologia , Epididimo/patologia , Masculino , Mitocôndrias/química , Distribuição Aleatória , Ratos , Ratos Wistar , Reishi/fisiologiaRESUMO
OBJECTIVE: To study the effect of endogenous carbon monoxide (CO) on the smooth muscle function of the dog penile corpus cavernosum in vitro. METHODS: Tissue bioassay was used to measure the corpus cavernosum muscle contraction and relaxation. The production of CO was induced in the corpus cavernosum smooth muscle, and the effect of CO on the penile corpus cavernosum smooth muscle pre-contracted by phenylephrine (PE) was determined. RESULTS: Chlorinous hemoglobin could relax the smooth muscle stripes pre-contracted by 10 micromol/L PE. A dose-dependent relaxation was observed. The relaxation responses by 10 -100 micromol/L chlorinous hemoglobin were significant compared with the control group (P < 0. 01). The pretreatment of the muscle stripes with ZnPP-IX or methylthioninium significantly reduced the relaxing effect of chlorinous hemoglobin (P < 0.01). CONCLUSION: The relaxing effect of endogenous CO on the smooth muscle of the penile corpus cavernosum depends on the concentration of endogenous CO. The underlying mechanism may involve the pathway from CO to cGMP production.
Assuntos
Monóxido de Carbono/fisiologia , Músculo Liso/fisiologia , Animais , Cães , Relação Dose-Resposta a Droga , Hemina/farmacologia , Técnicas In Vitro , Masculino , Músculo Liso/efeitos dos fármacos , Ereção Peniana/efeitos dos fármacos , Ereção Peniana/fisiologia , Pênis/efeitos dos fármacos , Pênis/fisiologiaRESUMO
OBJECTIVE: To observe the effects of Ganoderma lucidum spores on Cytochrome C (Cyt-C) and mitochondrial calcium in the testis of NIDDM rats. METHODS: Fifty male Wistar rats were divided randomly into three groups: model, ganoderma and normal control, the first two groups injected with 2% STZ through vena caudalis, and the last one with half-and-half sodium citrate/citrate buffer solution. Two weeks after normal diet, glucose tolerance tests were performed and the rats with abnormal glucose tolerance from the model and ganoderma groups received high-fat and high-carbohydrate food, the ganoderma group given Ganoderma lucidum spores (250mg/[ kg x d] ) in addition, both for 10 weeks. Glucose tolerance tests were repeated 1 day before the end of the experiment and the rats were castrated and relevant indexes measured. RESULTS: The NIDDM model was successfully constructed. In the model group, the levels of mitochondrial Cyt-C and mitochondrial calcium were significantly lower (P <0. 05) while that of the plasma Cyt-C was significantly higher than in the ganoderma and the control groups. CONCLUSION: Cyt-C and calcium ion are involved in the damage of the testis. Ganoderma lucidum spores can protect the testis of NIDDM rats.
Assuntos
Cálcio/metabolismo , Citocromos c/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Mitocôndrias/metabolismo , Reishi , Testículo/metabolismo , Animais , Masculino , Mitocôndrias/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar , Testículo/efeitos dos fármacosRESUMO
PURPOSE: CXCL3 and its receptor CXCR2 were considered to play particularly important roles in the progression of malignancies. However, the investigations about CXCL3/CXCR2 axis in prostate cancer have been poorly involved. Herein we firstly reported our studies on the expression and biological roles of CXCL3 and CXCR2 in prostate cancer. METHODS: Expression levels of CXCL3 and CXCR2 in prostate cancer cell lines (PC-3, DU145 and LNCaP), immortalized prostate stromal cell line (WPMY-1) and immortalized prostate epithelial cell line (RWPE-1) were investigated by RT-PCR, ELISA and western blot, whereas expression levels of CXCL3 in a prostate tissue microarray were detected by immunohistochemistry. Cell counting kit-8 and transwell assays were, respectively, utilized to determine the effects of exogenous CXCL3 on the cell proliferation and migration. We further examined whether CXCL3 could regulate the expression of genes correlated with prostate tumorigenesis by RT- PCR. RESULTS: Elevated expression of CXCR2 was detected in DU145, LNCaP and RWPE-1. Moreover, high-level CXCL3 can be secreted by PC-3 and RWPE-1, and CXCL3 protein expression level in tissue microarray is concordant with prostate cancer metastasis. Exogenous CXCL3 does not contribute to proliferation, but has a significant effect on migration of prostate cancer cells and RWPE-1. Finally, our data showed that exogenous CXCL3 can regulate the expression of genes including ERK, TP73, NUMB, BAX and NDRG3. CONCLUSION: Our findings suggest that CXCL3 and its receptor CXCR2 are overexpressed in prostate cancer cells, prostate epithelial cells and prostate cancer tissues, which may play multiple roles in prostate cancer progression and metastasis.
Assuntos
Quimiocinas CXC/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias da Próstata/genética , RNA Mensageiro/metabolismo , Receptores de Interleucina-8B/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quimiocinas CXC/metabolismo , Quimiocinas CXC/farmacologia , Células Epiteliais/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Próstata/citologia , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Receptores de Interleucina-8B/metabolismo , Células Estromais/metabolismo , Proteína Tumoral p73/genética , Proteína X Associada a bcl-2/genéticaRESUMO
OBJECTIVES: To evaluate the effects of varicocele (VC) on IL-1 and NO levels in testes of rats with VC. METHODS: Male adult Wistar rats were divided into two groups randomly, VC group (n = 30) and pseudo-operation group (n = 20), and the levels of IL-1 and NO in the testes were determined and compared. RESULTS: The levels of IL-1 and No of left tests in VC group were higher than those in pseudo-operation group, respectively(P < 0.01). While the levels of IL-1 and NO of right testes between two groups were not significantly different (P > 0.05). More over, the level of IL-1 correlated significantly with that of NO(r = 0.572, P < 0.01). CONCLUSIONS: The results revealed that the changes of IL-1 and NO levels in the testes of rats with VC might be the reason which caused testes damage, disturbance of spermatogenesis and even infertility.
Assuntos
Interleucina-1/metabolismo , Óxido Nítrico/metabolismo , Testículo/metabolismo , Varicocele/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar , Testículo/ultraestruturaRESUMO
PURPOSE: To investigate the mechanism of the anti-epileptic effect of Ganoderma lucidum polysaccharides (GLP), the changes of intracellular calcium and CaMK II α expression in a model of epileptic neurons were investigated. METHOD: Primary hippocampal neurons were divided into: 1) Control group, neurons were cultured with Neurobasal medium, for 3 hours; 2) Model group I: neurons were incubated with Mg(2+) free medium for 3 hours; 3) Model group II: neurons were incubated with Mg(2+) free medium for 3 hours then cultured with the normal medium for a further 3 hours; 4) GLP group I: neurons were incubated with Mg(2+) free medium containing GLP (0.375 mg/ml) for 3 hours; 5) GLP group II: neurons were incubated with Mg(2+) free medium for 3 hours then cultured with a normal culture medium containing GLP for a further 3 hours. The CaMK II α protein expression was assessed by Western-blot. Ca(2+) turnover in neurons was assessed using Fluo-3/AM which was added into the replacement medium and Ca(2+) turnover was observed under a laser scanning confocal microscope. RESULTS: The CaMK II α expression in the model groups was less than in the control groups, however, in the GLP groups, it was higher than that observed in the model group. Ca(2+) fluorescence intensity in GLP group I was significantly lower than that in model group I after 30 seconds, while in GLP group II, it was reduced significantly compared to model group II after 5 minutes. CONCLUSION: GLP may inhibit calcium overload and promote CaMK II α expression to protect epileptic neurons.
Assuntos
Anticonvulsivantes/uso terapêutico , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cálcio/metabolismo , Epilepsia/tratamento farmacológico , Hipocampo/patologia , Neurônios/enzimologia , Polissacarídeos/uso terapêutico , Reishi/química , Animais , Animais Recém-Nascidos , Anticonvulsivantes/farmacologia , Modelos Animais de Doenças , Epilepsia/enzimologia , Epilepsia/patologia , Fluorescência , Espaço Intracelular/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fitoterapia , Polissacarídeos/farmacologia , Ratos WistarRESUMO
Epilepsy can cause cerebral transient dysfunctions. Ganoderma lucidum spores (GLS), a traditional Chinese medicinal herb, has shown some antiepileptic effects in our previous studies. This was the first study of the effects of GLS on cultured primary hippocampal neurons, treated with Mg(2+) free medium. This in vitro model of epileptiform discharge hippocampal neurons allowed us to investigate the anti-epileptic effects and mechanism of GLS activity. Primary hippocampal neurons from <1 day old rats were cultured and their morphologies observed under fluorescence microscope. Neurons were confirmed by immunofluorescent staining of neuron specific enolase (NSE). Sterile method for GLS generation was investigated and serial dilutions of GLS were used to test the maximum non-toxic concentration of GLS on hippocampal neurons. The optimized concentration of GLS of 0.122 mg/ml was identified and used for subsequent analysis. Using the in vitro model, hippocampal neurons were divided into 4 groups for subsequent treatment i) control, ii) model (incubated with Mg(2+) free medium for 3 hours), iii) GLS group I (incubated with Mg(2+) free medium containing GLS for 3 hours and replaced with normal medium and incubated for 6 hours) and iv) GLS group II (neurons incubated with Mg(2+) free medium for 3 hours then replaced with a normal medium containing GLS for 6 hours). Neurotrophin-4 and N-Cadherin protein expression were detected using Western blot. The results showed that the number of normal hippocampal neurons increased and the morphologies of hippocampal neurons were well preserved after GLS treatment. Furthermore, the expression of neurotrophin-4 was significantly increased while the expression of N-Cadherin was decreased in the GLS treated group compared with the model group. This data indicates that GLS may protect hippocampal neurons by promoting neurotrophin-4 expression and inhibiting N-Cadherin expression.
Assuntos
Caderinas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Epilepsia/metabolismo , Hipocampo/metabolismo , Fatores de Crescimento Neural/metabolismo , Neurônios/metabolismo , Reishi/química , Animais , Caderinas/genética , Modelos Animais de Doenças , Epilepsia/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Fatores de Crescimento Neural/genética , Neurônios/efeitos dos fármacos , Ratos , Esporos Fúngicos/químicaRESUMO
<p><b>OBJECTIVE</b>To explore the expressions of HO-2 and CO in the corpus cavernosum of castrated rats in order to further study the pathogenesis of erectile dysfunction (ED).</p><p><b>METHODS</b>We randomly divided 72 male SD rats into four groups: normal control, sham operation, castration, and castration + ZnPP. We detected intracavernous pressure (ICP) and penile erection in the basic condition and after apomorphine (APO) induction, determined the expression of the HO-2 protein in the corpus cavernosum by laser scanning confocal microscopy, and measured the level of CO by spectrophotometry during different periods of penile erection.</p><p><b>RESULTS</b>The ICP in the basic condition and that after APO induction and the rate of penile erection were decreased significantly in the castration group ([11.68 ± 0.69] mmHg, [54.81 ± 3.86] mmHg, and 33.3%) and the castration + ZnPP group ([11.20 ± 0.71] mmHg, [41.17 ± 5.41] mmHg, and 22.2%) as compared with the normal control ([22.83 ± 2.66] mmHg, [66.92 ± 7.77] mm-Hg, and 100%) and the sham operation group ([23.35 ±2.22] mmHg, [70.43 ?7. 22] mmHg, and 100%) (all P <0. 01). After APO induction, ICP in the castration + ZnPP group was remarkably reduced in comparison with that in the castration group (P < 0.01), and so was the expression of the HO-2 protein before and during penile erection in the castration (445.4 ± 23.7 and 847.4 ± 35.0) and the castration + ZnPP group (390.1 ± 29.7 and 526.0 ± 52.5) compared with the normal control (512.7 ±57.4 and 1145.2 ± 89.8) and the sham operation group (583.7 ± 8.0 and 1016.3 ± 79.8), the expression of the HO-2 protein significantly decreased in the castration group (445.4 ± 23.7 and 847.4 ± 35.0) (P < 0.05 or 0.01), markedly lower in the castration + ZnPP than in the castration group during penile erection (P < 0.01) but with no significant differences among the four groups after it. Before, during and after penile erection, the levels of CO were remarkably decreased in the castration ([20.59 ± 1.01], [32.53 ± 1.26], and [18.71 ± 1.22] x 10(-7) nmol/L) and the castration +ZnPP group ([12.52 ± 1.05], [21.90 ± 1.02], and [16.56 ± 0.55] x 10(-7) nmol/L) as compared with the normal control ([26.76 ± 1.41], [48.25 ± 1.01], and [27.10 ± 1.58 ] x 10(-7) nmol/L) and the sham operation group ([25.41 ± 2.09], [ 47.90 ± 1.22], and [25.67 ± 1.20] x 10(-7) nmol/L) (P < 0.05 or 0.01), significantly lower in the castration + ZnPP than in the castration group during penile erection (P < 0.01).</p><p><b>CONCLUSION</b>Decreased expressions of HO-2 and CO may correlate with erectile dysfunction in castrated rats.</p>
Assuntos
Animais , Humanos , Masculino , Ratos , Apomorfina , Farmacologia , Monóxido de Carbono , Metabolismo , Agonistas de Dopamina , Farmacologia , Disfunção Erétil , Chaperonas Moleculares , Metabolismo , Orquiectomia , Ereção Peniana , Pênis , Metabolismo , Distribuição Aleatória , Ratos Sprague-DawleyRESUMO
The concentrations of 7 heavy metals (Ni, Cu, Cr, Pb, Cd, As, Hg) and organic matters in the surface sediments of Liao River were determined by atomic absorption spectrometry (AAS) and atomic fluorescence spectrometry (AFS), and sediments pollution assessment was carried out using geoaccumulation index. Moreover, the sources of heavy metal contamination were estimated with the principal component analysis (PCA). The results demonstrate that the heavy metal concentrations of Liao River are markedly higher than that of Liao River in 1998 and lay at medium level compared with other rivers in China. The average concentrations (mg/kg) obtained were: Ni 26.5 mg x kg(-1), Cu 37.9 mg x kg(-1), Cr 90.3 mg x kg(-1), Pb 32.9 mg x kg(-1), Cd 0.49 mg x kg(-1), As 12.3 mg x kg(-1), Hg 0.14 mg x kg(-1). The results of geoaccumulation index reveal that sediments of Liao River are uncontaminated with Ni, As, lightly contaminated with Cu, Cr, Pb and moderately contaminated with Cd, Hg. The order of the analyzed heavy metals, arranged from the highest to lowest pollution degree, is as follows Cd > Hg > Cu > Cr > Pb > As > Ni. By estimating the sources of heavy metal contamination with the Principal component analysis (PCA), it was found that the first two components account for 58.74% and 17.18% of the total variance, respectively. The industrial and living wastewater, degradation of organic matter atmospheric precipitation and geochemical changes are the main sources of heavy metal contamination.
Assuntos
Poluição Ambiental/análise , Sedimentos Geológicos/análise , Metais Pesados/análise , Rios , Poluentes Químicos da Água/análise , China , Poluentes Químicos da Água/químicaRESUMO
Three kinds of thiol collector, sodium diethyldithiocarbamate (DDTC), potassium ethyl xanthate (EXT) and ammonium dibutyl dithiphosphate (DDTP), were adopted to stabilize heavy metals from municipal solid waste incineration fly ash (MSWI fly ash). The concentration of the three thiol collectors was all 62.5 micromol x g(-1) fly ash. Scanning electron microscopic observation shows that, the thiol collectors evenly cover on the surface of fly ash which makes the angles of mineral crystal ambiguous. Furthermore, the leaching characteristics of heavy metal Cu, Pb, Cd, Cr and Zn in fly ash were analyzed according to the toxicity characteristic leaching procedure (TCLP) and the horizontal vibration method. Comparing with Na2S, thiol collectors present better stabilization effects for Cu and Pb when the extractant is 0.1 mol x L(-1) acetic acid. DDTC stabilizes almost all the acid-extractable Cu, and DDTP stabilizes 69.2% of acid-extractable Pb. When extracted by water, the stabilization ratios of the five heavy metals by DDTC, EXT and DDTP are 72.6%, 73.5% and 76.8%, respectively, significantly higher than that by Na2S (52.4%). The affinity preference of the thiol collectors for the five heavy metals is generally in the order of Cu > Pb > Cr > Cd > Zn. Also, over 60% of the collector participates in the chelating reaction with the acid-extractable heavy metals. Under neutral and alkali condition (pH > 6) the chelators of heavy metal-thiol collector are steady, but partly dissolved under acid condition (pH < 6). Evidently, in order to obtain better heavy metal stabilization effects, it is important to maintain the acid buffer capacity of stabilized fly ash at a higher level.