糖尿病大鼠血、尿、肾脏内皮素变化及意义

Contents and significance of endothelin in plasma urine and renal tissue of diabetic rats

目的 探讨内皮素在糖尿病大鼠血浆、尿、肾脏中的含量变化和意义。方法 采用链脲佐菌素 (STZ)诱导大鼠糖尿病模型 ,观察 12周时肾脏损害和血浆、尿、肾脏组织内皮素 (ET)的变化。结果 与正常对照大鼠相比 ,糖尿病大鼠 12周时体重降低 ,内生肌酐清除率 (Ccr)、血尿素氮 (BUN)、2 4h尿蛋白排泄量 (UPE)明显升高。电镜可见细胞外基质堆积和基膜增厚。血浆ET明显降低 ,而肾组织ET含量、2 4h尿ET排泄量 (UET)显著升高 (P <0 0 1)。结论 12周糖尿病大鼠已有明显肾脏病变。研究提示肾脏ET的合成增加参与了糖尿病肾病的发生 ,高血糖的直接作用可能为抑制内皮细胞合成、释放内皮素。

Objective To observe the contents of endothelin(ET) in plasma urine and renal tissue of diabetic rats and their significance. Methods Diabetic mellitus was induced by an intraperitoneal injection of streptozotocin (50 mg/kg) in rats. Renal damages and changes of endothelin in plasma, urine and renal tissue were observed. Results After 12 weeks of hyperglycemia, endogenous creatinine clearance rate, blood urea nitrogen, and 24 hour urinary protein excretion increased significantly and the body weight decreased in the diabetic rats when compared with controls. Extracellular martix accumulation and basement membrane thickening were seen with EM. Plasma ET of diabetic rats was lower than that of normal rats, but renal tissue ET and 24 hour urinary ET excretion were increased obviously. Conclusion Our study suggests: ①Increase of renal ET synthesis plays an important role in the pathogensis of diabetic nephropathy. ②Hyperglycemia has direct effect on the inhibition of the synthesis and release of endothelin in endothelial cells. ③The increased urine ET excretion in diabetes mellitus is related to the severity of the diabetic renal lesion and can be regarded as an early and sensitive marker of diabetic nephropathy.