替米沙坦对糖尿病大鼠肾脏肾素受体表达的影响

目的：研究替米沙坦对链脲佐菌素糖尿病大鼠肾脏肾素受体表达的影响。方法：18只雄性Wistar大鼠随机分为对照组（N组）、糖尿病组（DM组）、替米沙坦组（T组）。大鼠左下腹腔注射链脲佐菌素60mg·kg-1建立糖尿病模型。测定第4，8周尿蛋白。8周后心脏取血检测血糖、血肌酐、血钠、血钾；取肾脏行PAS染色观察病理改变；免疫组化检测肾脏肾素受体表达水平；RT—PCR检测肾脏肾素受体mRNA表达水平；western blot检测肾素受体表达情况。结果：4周和8周时DM组大鼠24h尿蛋白较N组显著升高（P〈0．05或P〈0．01），T组24h尿蛋白与DM组相比明显降低（P〈0．01）；DM组8周时肾小球损伤指数明显高于N组（P〈0．05），T组则明显低于DM组（P〈0．05）；免疫组化、RT—PCR以及Westernblot检测显示T组肾素受体表达较DM组显著降低（P〈0．05），而N组和DM组肾素受体表达没有明显差异（P〉0．05）。结论：替米沙坦可能部分通过抑制肾素受体的表达减轻早期糖尿病大鼠肾脏损伤。

Telmisartan on the Expression of Renin Receptor in the Kidneys of Diabetic Rats

Objective： To investigate the Telmisartan on the expression of renin receptor in the kidneys of streptozotocin-induced rats. Method： Eighteen male Wistar rats were randomly assigned to normal control group （n = 6, group N）, diabetic group （n = 6, group DM） and telmisartan group（ n =6, group T）. Streptozotocin（ 60 mg.kg-1 ） was administrated intraperitoneally to induce diabe- tes in rat. Urine creatinine and proteinuria were measured at week 4, 8. At week 8 animals were sacrificed and blood glucose, serum creatinine （ SCr）, serum sodium and serum potassium were assayed. Renal pathological changes were quantified with glomerular injury index on PAS-staind sections. Protein and mRNA levels of renin receptor expression were analyzed by immunohistochemical staining, RT-PCR and western blot. Result： The proteinuria and glomerular injury index in diabetic rats were significantly increased when com- pared to those in normal rats at week 8. Protein and mRNA expression of renin receptor in kidneys of telmisartan group was down-regu- lated, however, renin receptor expression was comparable between normal control group and diabetic group. Conclusion： Telmisartan might alleviate renal injury partly throuth inhibiting expression of renin receptor in kidneys of early diabetic rats.