Effect Of Telmisartan And Insulin On The Expression Of Endoplasmic Reticulum Stress And Sirt1 In The Testis Of Type 1 Diabetic Rats

Objective:To observe the regulation effect of insulin or telmisartan on the expression of chop,GRP-78,caspase-12 and Sirt1 in the testes of type 1 diabetic rats.To explore the protective effect and mechanism of insulin or telmisartan on the testicular tissue of diabetic rats.Methods:Thirty-six male Sprague-Dawley(SD)rats were divided into normal control group(group A,n=8)and diabetic model group(n=28)randomly,which were induced by a single intraperitoneal injection of streptozotocin(STZ).There were twenty-four rats induced successfully.All these were divided into diabetic group(group B,n=8),diabetic treated with insulin group(group C,n=8)and diabetic treated with telmisartan group(group D,n=8).Rats in group C were given protamine-zinc insulin by subcutaneous injection once daily to control blood glucose at about 10mmol/l.The rats in group D were given telmisartan once a day by gavage.The rats in group A and group B were given equal volume of normal saline by gavage.Only at the end of the eighth week,can specimens be taken.At the same time,some tasks had to be done,and then the bilateral testes were took out and the epididymis was cut to prepared sperm suspension.The tresticular tissues were immediately thrown into the liquid nitrogen and then stored in the? 70C° refrigerator until analyses were carried out.The levels of testosterone were detected by radioimmunoassay,and calculat the weight and index of testicle,account thequantity and activity rate of sperm.The mRNA expression levels of chop,GRP-78,caspase-12 and Sirt1 were assessed by real-time fluorescent quantitative PCR.Results:1.The levels of blood glucose[(5.11±0.23)vs(27.38±0.82)mmol/l,P<0.05] were remarkably increased in group B than those in group A,testosterone[serum testosterone(1.60±0.38)vs(3.75±1.01)ng/ml,testicular testosterone(0.45±0.12)vs(3.31±0.26)pg/?g protein,all P<0.05],testes weight[(1.79±1.10)vs(3.23±0.49)g,P<0.05],sperm counts[(38.25±3.06)vs(34.38±3.58)x106 ?/mL,P<0.05] and motility [83.13±3.68)vs(74.38±7.01)%,P<0.05] were significantly decreased in group B than those in group A.The mRNA expression levels expression of testicular chop,GRP-78,caspase-12[(1.33±0.04)vs(1.00±0.00)?(1.64±0.16)vs(1.00±0.00)?(1.55±0.13)vs(1.00±0.00),? P<0.05]were remarkably increased in group B than those in group A.However,the level of the mRNA expression of testicular Sirt1[(0.52±0.04)vs(1.00±0.00),P<0.05] was significantly decreased.2.After insulin therapy,the levels of blood glucose [(9.71±0.23)vs(27.38±0.82)mmol/l,P<0.05] were significantly decreased in group C than those in group B,testosterone[serum testosterone(2.48±0.57)vs(1.60±0.38)ng/ml,testicular testosterone(3.11±0.63)vs(0.45±0.12)pg/?g protein,all P<0.05],testes weight[(3.05±0.36)vs(1.79±1.10)g,P<0.05],sperm counts [(34.38±3.58)vs(7.75±1.67)x106 ?/mL,P<0.05]and motility [(74.38±7.01)vs(19.25±2.38)%,P<0.05] were significantly increased in group C than those in group B.The levels of the mRNA expression of testicular chop,GRP-78,caspase-12 were significantly decreased than those in group B[(0.98±0.06)vs(1.33±0.04)?(1.21±0.08)vs(1.64±0.16)?(1.24±0.10)vs(1.55±0.13),all P<0.05].The level of the m RNA expression of testicular Sirt1 was significantly increased than those in group B [(0.83±0.09)vs(0.52±0.04),P<0.05].3.After telmisartan therapy,the levels of blood glucose [(21.28±0.54)vs(27.38±0.82)mmol/l,P<0.05] were significantly decreased in group D than those in group B,sperm counts[(11.1±2.03)vs(7.75±1.67)x106 ?/mL,P<0.05] andmotility[(30.13±3.83)vs(19.25±2.38)%,P<0.05] were significantly increased in group D than those in group B,but the levels of testosterone [serum testosterone(1.71±0.32)vs(1.60±0.38)ng/ml,testicular testosterone(0.58±0.10)vs(0.45±0.12)pg/?g protein,all P>0.05] and testes weight[(2.16±0.99)vs(1.79±1.10)g,P>0.05] had no significant changes.The levels of the mRNA expression of testicular chop,GRP-78,caspase-12 were significantly decreased in group D than those in group B [(1.29±0.04)vs(1.33±0.04)?(1.36±0.12)vs(1.64±0.16)?(1.33±0.09)vs(1.55±0.13),all P<0.05].The level of the mRNA expression of testicular Sirt1 was significantly increased [(0.69±0.07)vs(0.52±0.04),P<0.05].4.The index of testes had no statistical significance difference among four groups[(0.94±0.20)vs(1.07±0.52)?(0.73±0.08)vs(0.94±0.201)?(0.73±0.08)vs(1.07±0.52)?(1.03±0.39)vs(0.94±0.201)?(1.03±0.39)vs(1.07±0.52)(P>0.05)].Conclusion:1.The levels of the expression of testicular chop,GRP-78,caspase-12 were increased and the level of the expression of testicular Sirt1 was decreased in diabetic group,which plays an important in the occurrence of testicular pathological changes.2.Insulin or 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.