缬沙坦对糖尿病大鼠动脉Toll样受体4和髓样分化因子88表达的影响

Effect of valsartan on the expressions of Toll-like receptor 4 and myeloid differentiation factor 88 in the arteries of diabetic rats

目的研究选择性血管紧张素Ⅱ受体拮抗剂缬沙坦对糖尿病大鼠动脉血管组织Toll样受体4（TLR4）和髓样分化因子88（Myd88）表达的影响。方法31只SD大鼠随机分为正常对照组（n=7），糖尿病组（n=12）和缬沙坦组（n=12）。用链脲佐菌素诱导的糖尿病大鼠模型成功后，给予缬沙坦20mg·kg^-1·d^-1灌胃。观察各组大鼠的血糖、体重。于12周时用免疫组化、RT—PCR和Western印迹法检测3组大鼠动脉血管组织中TLR4和Myd88的表达。结果糖尿病和缬沙坦组大鼠体重较正常对照组明显降低（均P〈0．01），糖尿病和缬沙坦组间血糖差异无统计学意义（P〉0．05）；糖尿病组大鼠血管组织中TLR4和Myd88 mRNA与蛋白的表达明显高于正常对照组（均P〈0．01），而缬沙坦组明显低于糖尿病组（均P〈0．01）。结论缬沙坦降低糖尿病大鼠动脉血管组织中TLR4和Myd88表达，可能对糖尿病血管早期的炎性改变起防治作用。

Objective To investigate the effect of valsartan on the expressions of toll-like recpter 4 （TLR 4） and myeloid differentiation factor 88 （Myd88） in the arteria of diabetic rats. Methods Thirtyone Sprague-Dawley rats were randomly divided into normal control group（n = 7）, diabetes mellitus group （n=12） and valsartan group （n-12）. Diabetic rats induced by a single injection of streptozotocin were treated with valsartan 20 mg · kg^-1· d^-1 intragastrically. The blood glucose and body weight were monitored periodically. The expressions of TLR4, Myd88 mRNA and protein in the arteria of the rats at 12th week were analyzed by RT-PCR, immunohistochemistry and Western blotting. Results The body weight of rats in diabetes mellitus and valsartan groups decreased significantly compared with that in normal control group （P〈 0.01）, but no significant difference in blood glucose was found between diabetes mellitus and valsartan groups （P〉0.05）. The expressions of TLR4 and MyD88 mRNA and protein in diabetes mellitus group were significantly increased as compared with normal control group（both P〈0.01）, but decreased after valsartan treatment （P〈0.01）. Conclusions Valsartan significantly reduces the expressions of TLR4 and MyD88 in the arteria of diabetic rats, suggesting that may be useful for preventing or treating early inflammation in the arteria of diabetic rats.