ADM、NO及ADMR表达在糖尿病肾病中的变化及作用

Alterations and role of adrenomedullin,nitric oxide and adrenomedullin receptor expression in diabetic nephropathy

目的探讨肾上腺髓质素(ADM)、一氧化氮(NO)及肾上腺髓质素受体(ADMR)在大鼠糖尿病肾病(DN)中的变化及作用。方法采用腹腔注射链脲佐菌素(STZ)制备糖尿病大鼠动物模型,随机分为对照组、糖尿病2周和4周组;采用RT-PCR和免疫组织化学方法检测肾皮质的AD-MRmRNA和蛋白的表达;同时检测大鼠的血糖、尿白蛋白排泄率(UAER)、尿量、肾重/体质量,以及肾皮质ADM与NO水平。结果注射STZ诱导糖尿病发生2周、4周后,与同批正常对照组比较,糖尿病组大鼠肾皮质的ADM、NO水平显著升高(P<0.01),肾皮质的ADMRmRNA和蛋白表达显著升高(P<0.05)。结论糖尿病大鼠早期就有ADM、ADMR和NO的异常改变。提示ADM、ADMR以及NO可能参与糖尿病肾病的发生、发展过程。

Objective To search for the changes and role of the levels of adrenomedullin（ADM）,nitric oxide（NO）and the expression of adrenomedullin receptor（ADMR）in the kidney of diabetic rats.Methods Male Wistar rats（180±20g body weight）were allocated to two groups which were the control group and non-diabetic rats group.Diabetes mellitus（DM）group,STZ-induced diabetic rats（STZ 60mg/kg,i.p.）.The levels of ADM in renal cortex and urine albumin excretion ratio（UAER）were measured by radioimmunoassay（RIA）,while renal cortex nitric oxide（NO）was measured by colorimetric assay.The expression of ADMR was measured by RT-PCR and Immunohistochemistry（IHC）.Blood glucose,body weight,kidney weight,urine volume were measured.Results Compared with control group on same time,diabetic rats were associated with enhanced ADM and NO level in renal cortex（P0.01）.The expression of ADMR mRNA and protein was significantly upregulated on renal cortex（P0.05）.Conclusion The results display that there are changes with the level of ADM and NO in renal cortex,also the expression of renal cortical ADMR in diabetic rats.These results imply that the ADM,ADMR and NO may contribute to the pathogenesis and development of diabetes mellitus and diabetic complication.