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Objective To analyze the effect of exogenous recombinant spherical adiponectin on the autophagy and endoplasmic reticulum stress in testis of diabetic mice induced by streptozotocin, and explore the mechanism of such protective effect to the testis of diabetic mice. Methods Forty-eight male C57BL/6 mice were randomly divided into normal control group (NC, n=8) and diabetes group (n=40). Diabetic mouse model was established by intraperitoneal injection of streptozotocin, and 24 mice were successfully established. Diabetic mice were randomly divided into diabetic group (DM, n=8), diabetic adiponectin low dose group (DLA, n=8), and diabetic adiponectin high dose group (DHA, n=8). Mice in DLA group and DHA group were given intraperitoneal injection of recombinant spherical adiponectin at dose of 5 μg/(kg·d) and 15 μg/(kg·d) respectively. Mice in NC group and DM group were given intraperitoneal injection of the same amount of normal saline. After 8 weeks of adiponectin treatment, blood samples were taken to measure fasting blood glucose with glucose oxidase method. Enzyme-linked immunosorbent assay (ELISA) was performed to determine serum testosterone, insulin, follicular stimulating hormone (FSH) and luteinizing hormone (LH). Testicular weight was measured, and the testicular index (proportion by weight of testis/body) was calculated. Sperm count and mobility were measured. Morphological changes of testicular tissues were observed by HE staining. The mRNA expressions of endoplasmic reticulum stress (GRP78, CHOP, Caspase-12) and autophagy (LC3, Beclin1 and p62) were determined by real-time PCR. Results Compared with NC group, it was found in DM group that seminiferous tubules were deformed, the number of spermatogenic cells and Sertoli's cells reduced, the number of sperm in the tubular lumen reduced, and spermatogenic cells sloughed in some tubular lumens. The body weight, testicular weight, sperm motility, sperm count, and the levels of serum insulin, testosterone, LH and FSH significantly decreased in DM group than those in NC group (P

Objective To observe the regulation effect of insulin and telmisartan on the endoplasmic reticulum stress (ERS) and the expression of silent information regulator 1 (Sirt1) in the testes of type 1 diabetic rats, and explore the protective effect and mechanism of insulin and telmisartan on the testicular tissue of diabetic rats. Methods Male Sprague-Dawley (SD) rats were randomly divided into normal control group (group A, n=8), diabetic control group (group B, n=8), diabetic treated with insulin group (group C, n=8) and diabetic treated with telmisartan group (group D, n=8). Diabetic rats were induced by a single intraperitoneal injection of streptozotocin. Rats in group C were subcutaneously injected with protamine-zinc insulin once a day, and in group D were given telmisartan once a day by gavage. Only at the end of the eighth week can specimens be taken. And then some tasks were performed such as calculating the testicular weight and testis index, accounting the quantity and activity rate of sperm, detecting the testosterone levels and mRNA expression levels of CCAAT/enhancer binding protein homologous protein (CHOP), glucose regulated protein (GRP-78), cysteine aspartic acid specific protease 12 (caspase-12) and Sirt1. Results The levels of testosterone, testes weight, sperm counts and motility significantly decreased in group B than in group A (P0.05). The mRNA expression levels of testicular CHOP, GRP-78 and caspase-12 significantly decreased (P0.05). Conclusion Insulin and telmisartan may play a protective role on testicular tissues by down-regulating the expression of endoplasmic reticulum stress and up-regulating the expression of Sirt1. DOI: 10.11855/j.issn.0577-7402.2016.10.03

Objective To explore the mechanisms of telmisartan in regulating the expression of adiponectin receptor 1 (AdipoR1) in diabetic cardiomyocytes. Methods Investigation of the inhibitory effects of AngⅡ were performed in 3 subexperiments as follows: One detects mRNA and protein expression of AdipoR1 in different batches of H9C2 cells pre-treated with AngⅡ for 48 hours at a concentration of 0, 10-8, 10-7, 10-6, 10-5mol/L respectively, one in cells pre-treated with AngⅡ at a concentration of 10-7mol/L for 0, 12, 24, 36 and 48 hours respectively, while the last in cells pre-treated with telmisartan at 10-5mol/L for 1 hour followed by AngⅡ at 10-7mol/L for 24 hours. Cultured H9C2 cardiomyocytes were randomly divided into following five groups: normal control group (NG), high glucose group (HG), high glucose plus telmisartan group (HG+T), high glucose plus telmisartan and PPAR-γ antagonist GW9662 group (HG+T+GW), and normal glucose plus mannitol group (NG+M). Cardiomyocytes in the above-mentioned five groups were continued to be cultured for 24h, then the mRNA and protein expressions of AdipoR1 in cardiomyocytes were assayed. Fluorescent quantitative real-time PCR and Western blotting were used respectively to analyze the mRNA and protein expressions of AdipoR1 in cardiomyocytes. Results The mRNA and protein expressions of AdipoR1 in cardiomyocytes were significantly decreased by AngⅡ at concentrations of 10-8, 10-7, 10-6 and 10-5mol/L (P0.05). The mRNA and protein expressions of AdipoR1 in cardiomyocytes were significantly up-regulated in group HG+T compared with that in group HG (P

Objective To explore the effect of telmisartan on the expression of NADPH oxidase subunits p22phox and NOX4 in the myocardiam of type 2 diabetic rats.Methods Thirty-six male Wistar rats were randomly divided into two groups: normal control group(group A,n=10),diabetic model group(n=26).Type 2 diabetic model was established by high-fat and high-sugar diet followed by intraperitoneal injection of a low dose of streptozotocin(STZ).After the model was reproduced successfully,20 diabetic rats were randomly divided into diabetic subgroup(group B,n=10) and telmisartan-treated subgroup(group C,n=10).Rats in group C were orally administered telmisartan(5mg/kg/d),and rats in group A and B were given equivalent volume of normal saline.All rats were sacrificed 12 weeks after treatment.The mRNA expressions of myocardial p22phox and NOX4 were detected by real-time fluorescence quantitative PCR,and the protein expressions of myocardial connective tissue growth factor(CTGF) and copper-zinc-superoxide dismutase(Cu-Zn-SOD) were detected by immunohistochemical staining.Results Compared with group A,the ratio of heart/body weight,the mRNA expression of myocardial p22phox and NOX4,and the protein expression of myocardial CTGF increased significantly in group B,and the protein expression of myocardial Cu-Zn-SOD decreased significantly(P < 0.05).The ratio of heart/body weight,the mRNA expression of myocardial p22phox and NOX4,and the protein expression of myocardial CTGF decreased significantly in group C than in group B(P < 0.05),and the protein expression of myocardial Cu-Zn-SOD increased significantly in group C when compared with that of group B(P < 0.05),but no significant difference of the above indexes was found between group A and C(P > 0.05).Conclusions Telmisartan can down-regulate the over-expression of myocardial NOX4 and p22phox mRNA in type 2 diabetic rats,lessen the myocardial damage induced by oxidative stress,thus plays a protective role in the myocardium of diabetic rats.