内皮素受体拮抗剂益米乐对糖尿病大鼠肾脏的保护作用

目的　探讨内皮素受体拮抗剂益米乐对糖尿病大鼠肾脏病变的保护机制。方法　选择健康雄性Wistar大鼠 42只,随机分为正常对照组(N组 )、糖尿病模型组 (D组 )、益米乐治疗组 (Y组 ) 3组,每组 14只。D组在大鼠腹腔注射链脲佐菌素建立糖尿病动物模型,Y组在建立糖尿病模型后,给予益米乐注射液 50mg·kg-1·d-1,N组和D组肌注等量的生理盐水。实验 4周、8周后,取大鼠的尿、血、肾组织标本,行生化及PCR检测。结果　3组间大鼠体重、肾重 /体重、血压、血糖、24小时尿蛋白定量、血肌酐、尿素氮差异均有显著意义(P<0. 05或P<0. 01)。肾组织降钙素基因相关肽(CGRP)和内皮素(ET)的mRNA表达差异有显著意义 (P<0. 05 )。结论　益米乐通过抑制ET 1的分泌,促进CGRP的合成,从而减轻CGRP与ET的失衡,对糖尿病肾病有明确的保护作用。

The protection effect of Yimile-an antagonist of endothelin receptor on the kidney of diabetic rats

Objective To investigate the protection mecha ni sm of Yimile which is an antagonist of endothelin(ET) receptor on the Wistar rat s with diabetic nephropathy.Methods 42 healthy male Wistar rats were randomly divided into three groups,normal group, diabetic model group and treatment group,14 rats in each group.The diabetic model was made by injecting S TZ into the abdomen of rats.The rats in treatment group were given with Yimile i njection 50 mg·kg -1 ·d -1 .The rats in normal group and diabetic mode l group were injected with equal quantity NS.On the 4th and 8th week after expe riment,the rats' urine,blood,kidney tissue were collected and detected by bioche mistry and PCR.Results There were significant differences in bo dy weight,kidney/body weight,BP,blood glucose,urinary protein quantity of 24 hou rs,SCR and BUN among three groups (P<0.05 or P<0.01).There were signif icant differences in the mRNA expressions of calcitonin -gene-related peptide (CGRP) and endothelin (ET) in kidney tissue among three groups (P<0.05). Conclusion Yimile has definite protection effect on diabetic nephr opathy by inhibiting the secretion of ET-1,promoting the composition of CGRP,re lieving the unbalance of CGRP and ET.