伊贝沙坦对糖尿病大鼠一氧化氮系统及肾脏的影响

The effects of irbesartan on nitric oxide system and kidney in diabetic rats

目的 研究伊贝沙坦对糖尿病大鼠一氧化氮 (NO)系统及肾脏的影响。 方法 随机将 4 0只Wistar大鼠分为 4组 ,每组 10只 ,分别为正常对照组、糖尿病组、伊贝沙坦组和开搏通组。病程 12周时处死大鼠 ,取血、尿和肾脏标本 ,测定尿量、体重、肾重 /体重比值、血糖、糖化血红蛋白(HbA1c) ;测定血清、尿液和肾组织的NO水平 ,通过免疫组化方法 ,检测肾脏组织诱导型一氧化氮合酶 (iNOS)蛋白的合成 ,并通过光镜和电镜观察肾脏的病理结构变化。 结果 治疗 12周后 ,糖尿病各组大鼠的尿量、肾重 /体重比值、血糖、HbA1c、血清、尿液和肾脏组织的NO水平、肾脏组织iNOS蛋白的合成、肾小球体积和肾小球基底膜厚度明显高于或大于正常组 ,体重明显低于正常组 (P <0 .0 1) ;伊贝沙坦组大鼠的血清、尿液和肾脏组织的NO水平、肾脏组织iNOS蛋白的合成、肾小球体积和肾小球基底膜厚度比糖尿病组明显减少 (P <0 .0 5 ) ;血清、尿液和肾组织NO水平与肾小球体积和肾小球基底膜厚度呈正相关。 结论 伊贝沙坦能延缓糖尿病大鼠肾脏功能损害的进展 ,其机制可能与伊贝沙坦不同程度地抑制糖尿病大鼠NO的产生有关。

Objective To investigate the effects of irbesartan on nitric oxide (NO) system and kidney in diabetic rat. Methods Forty adult male Wistar rats were randomly divided into four groups: control group, diabetes group, irbesartan group and captopril group. At the end of 12 weeks, the rats were sacrificed. Urine volume, body weight, ratio of kidney weight to body weight, plasma glucose and glycosylated hemoglobin (HbA 1c) were measured. The levels of NO of serum, urinary and renal tissues were determined. The inducible nitric oxide synthase (iNOS) of rats renal tissues were also determined by immunohistochemical method. The structure of renal tissue was observed by optical microscope and electron microscope, and the average volume of glomeruler and the average thickness of glomerular basement membrane were measured. Results Urine volume, ratio of kidney weight to body weight, plasma glucose, HbA 1c, NO levels of serum, urinary and renal tissue, average volume of glomeruler and the average thickness of glomerular basement membrane in diabetic rats were significantly greater than those of normal controls ( P <0.01), but body weight was lower than those of normal controls ( P <0.01). NO levels of serum, urinary and renal tissue in rats of irbesartan and captopril groups were significantly less than those of diabetic rats ( P< 0.01). There were positive relationships among NO levels of serum, urinary, renal tissue and average volume of glomeruler and the average thickness of glomerular basement membrane. Conclusion Irbesartan could prevent the injury of renal structure and function in STZ induced diabetic rats. And it may be one of the most important mechanisms that irbesartan could reduce the NO levels in STZ induced diabetic rats.