Effect Of Telmisartan On The Expression Of Adiponectin And Its Receptors In The Testes Of Type 1 Diabetic Rats

Objective:To observe the effect of telmisartan on the expression of adiponectin, adiponectin receptor and its signal transduction pathway AMPK, Akt/e NOS/NO in the testis of type 1diabetic rats. To investigate the possible protective mechanisms of telmisartan on the testis of type 1 diabetic rats.Methods:Twenty-seven male SD rats were randomly divided into normal control group(group NC, n=8) and diabetic model group(n=19). Diabetes was induced by intraperitoneal injection of streptozotocin(STZ). Sixteen successfully-induced diabetic rats were randomly divided into diabetic control(group DM, n=8) and diabetic treated with telmisartan(DT,n=8). The rats in group DT were given telmisartan by gavage. The rats in NC group and DM group were given equal volume of normal saline by gavage. At the end of the eighth week of telmisartan treatment, rats were sacrificed after blood samples were collected, and then the bilateral testes were took out and the epididymis was cut to prepared sperm suspension. Blood samples were used to detect related index. A part of tresticular tissues were fixed in neutral 40% formaldehyde solution and processed for histological analysis.The rest part of tresticular tissues were immediately thrown into the liquid nitrogen and then stored in the﹣70C° refrigerator until analyses were carried out. The levels of insulin and sex hormone were detected by radioimmunoassay. The levels of adiponectin, IL-6 and TNF-α were assayed by ELISA. The m RNA expression of testicular adiponectin and its receptors was assessed by real-time fluorescent quantitative PCR. The protein expressions of testicular adiponectin, adiponectin receptors,AMPK、P-AMPK、AKT、P-AKT andV e-NOS were analyzed by Western blot.Results:1. Testis weight, index of testis, sperm number and sperm motilityThe levels of testis weight, sperm number and sperm motility were significantly decreased in group DM than those in group NC(P<0.05), There was no significant difference in the level of index of testis between group DM and group NC(P>0.05). After telmisartan treatment for 8 weeks. There was no significant difference in the level of testis weight and index of testis between group DT and group DM(P>0.05), the levels of sperm number and sperm motility were significantly increased in group DT than those in group DM(P<0.05).2. Blood glucose, total cholesterol, triglyceride, free fatty acids, sex hormone, insulin,adiponectin, testicular NO、IL-6、TNF-αThe levels of blood glucose, TCH, TG, FFA, testicular NO、IL-6、TNF-α were significantly increased in group DM than those in group NC(P<0.05), the levels of serum and testicular testosterne,serum and testicular adiponectin,insulin were significantly decreased in group DM than those in group NC(P<0.05), there was no significant difference in the levels of LH and FSH(P>0.05). After telmisartan treatment for 8weeks,the levels of blood glucose, TCH, TG, FFA, testicular NO、IL-6、TNF-α were significantly decreased in group DM than those in group NC(P<0.05), the levels of serum and testicular adiponectin were significantly increased in group DT than those in group DM(P<0.05). there were no significant difference in the levels of serum and testicular testosterne, insulin, LH and FSH(P>0.05).3. The morphological observation of rats’ testis by HE stainIn group NC, testis seminiferous tuble and spermatogenic cellwere neatly arranged,mang sperms can be seen in the lumina. In group DM, testis seminiferous tuble atrophy or twist into irregular shape, with the lumen of vacuolar degeneration. the number of sperm cells on the wall significantly is less than control group, only close to the basement membrane of support cells and spermatogonial cells can be seen in indiviodualseminiferous, while the rest of the all levels of sperm cells and sperm disappeared, some or all of the sperm cells loss in seminiferous tuble, clogging in the lumen, or the sperm cells were disordered arrangement, the interstitial tissue proportion between seminiferous tubule was increased, but the interstitial cell shrinkage, cytoplasm was reduced, nucleus pycnosis,microvascular cavity occulsion and congestion in the interstitial tissue, inflammatory cell infiltrate in testicual interstitial. The testicular tissue degeneration in group DT was higher better than in group DM.4. The m RNA expression of testicular adiponection receptor 1 and adiponection receptor 2in each groupCompared with group NC, the m RNA expression of testicular adiponection receptor 1decreased significantly in group DM[(0.54±0.14)vs(0.71±0.15), P<0.05], there was no significant difference in the levels ofadiponection receptor 2 [(0.67±0.11)vs(0.77±0.16),P>0.05]. Compared with group DM, there were no significant difference in the m RNA expression of testicular adiponection receptor 1 and adiponection receptor 2 in group DT[(0.61±0.07)vs(0.54±0.14),(0.55±0.09)vs(0.67±0.11), P>0.05].5. The protein expression of testicular adiponectin and its receptors、P-AMPK/AMPK、P-AKT/Akt、e NOS.Compared with group NC,the protein expression of testicular adiponectin and adiponection receptor 1、P-AMPK/AMPK decreased significantly in group DM[(0.66±0.09)vs(1.00±0.00),(0.68±0.05)vs(1.00±0.00),(0.34±0.11)vs(1.00±0.00),P<0.05], the protein expression of P-AKT/Akt and e NOS increased significantly in group DM[(1.54±0.27)vs(1.00±0.00),(1.56±0.26)vs(1.00±0.00), P<0.05], adiponection receptor2 protein expression had no significant change in group DM.After telmisartan treatment,the protein expression of testicular adiponectin and adiponection receptor 1 increased significantly in group DT[(0.84±0.09)vs(0.66±0.09),(0.80±0.07)vs(0.68±0.05), P<0.05],the protein expression of P-AKT/Akt and e NOS decreased significantly in group DT[(1.24±0.39)vs(1.54±0.27),(1.16±0.47)vs(1.56±0.26), P<0.05], P-AMPK/AMPK and adiponection receptor 2 protein expression had no significant change in group DT[(0.65±0.52)vs(0.34±0.11),(1.02±0.15)vs(1.02±0.13), P>0.05].Conclusions:Telmisartan may reduce the injury degree on testes and play protective roles on testicular tissues in diabetic rats by regulating the expression of adiponectin, adiponectin receptor and the signal pathways mediated by adiponectin receptor.