替米沙坦和胰岛素对糖尿病大鼠睾丸内质网应激和沉默信息调节因子1表达的影响

Effect of telmisartan and insulin on endoplasmic reticulum stress and the expression of Sirt1 in testis of type 1 diabetic rats

目的观察替米沙坦和胰岛素对1型糖尿病大鼠睾丸组织内质网应激和沉默信息调节因子1(Sirt1)表达的影响,探讨替米沙坦和胰岛素对糖尿病大鼠睾丸的保护作用及其机制。方法健康雄性SD大鼠随机分为正常对照组(A组)、糖尿病对照组(B组)、糖尿病胰岛素治疗组(C组)和糖尿病替米沙坦治疗组(D组),每组8只。B、C、D组用链脲佐菌素制备1型糖尿病大鼠模型,C组大鼠每日皮下注射精蛋白锌胰岛素,D组每日给予替米沙坦灌胃。于实验第8周末留取标本,测定并计算睾丸重量及睾丸指数、精子数量及活动率,测定睾酮水平及睾丸组织中CCAAT增强子结合蛋白同源蛋白(CHOP)、葡萄糖调节蛋白-78(GRP-78)、半胱氨酸天冬氨酸特异性蛋白酶-12(caspase-12)、Sirt1 m RNA的表达水平。结果与A组比较,B组糖尿病大鼠睾酮水平、睾丸重量、精子数量及活动率明显降低(P<0.05),睾丸组织CHOP、GRP-78、caspase-12 m RNA表达水平明显升高(P<0.05),Sirt1 m RNA表达水平明显降低(P<0.05)。经胰岛素治疗后,C组大鼠血清睾酮、睾丸睾酮、睾丸重量、精子数量及活动率较B组明显升高(P<0.05),睾丸组织CHOP、GRP-78、caspase-12 m RNA表达水平较B组明显降低(P<0.05),Sirt1 m RNA表达水平较B组明显升高(P<0.05)。替米沙坦治疗后,D组大鼠精子数量、精子活动率较B组明显升高(P<0.05),血清睾酮、睾丸睾酮、睾丸重量与B组比较无明显变化(P>0.05),睾丸组织CHOP、GRP-78、caspase-12 m RNA表达水平均较B组明显降低(P<0.05),Sirt1 m RNA表达水平较B组明显升高(P<0.05)。4组大鼠睾丸指数比较差异无统计学意义(P>0.05)。结论替米沙坦和胰岛素通过下调内质网应激水平、上调Sirt1表达对糖尿病大鼠睾丸组织产生保护作用。

Objective To obser ve 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 m RNA 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（P〈0.05）. The m RNA expression levels of testicular CHOP, GRP-78 and caspase-12 remarkably increased（P〈0.05）, but the m RNA expression level of testicular Sirt1 significantly decreased（P〈0.05） in group B than in group A. After insulin therapy, the levels of serous and testicular testosterone, testes weight, sperm counts and motility significantly increased in group C than in group B（P〈0.05）. The m RNA expression levels of testicular CHOP, GRP-78 and caspase-12 decreased significantly（P〈0.05）, while the m RNA expression level of testicular Sirt1 significantly increased in group C than in group B（P〈0.05）. After telmisartan therapy, the sperm counts and motility significantly increased in group D than in group B（P〈0.05）, but the levels of serous and testicular testosterone and testes weight showed no significant changes（P〈0.05）. The m RNA expression levels of testicular CHOP, GRP-78 and caspase-12 significantly decreased（P〈0.05）, but the m RNA expression level of testicular Sirt1 significantly increased（P〈0.05） in group D than in group B. The testes index showed no significant difference among the four groups（P〈0.05）. 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.