糖尿病肾小球内非酶糖化与苯那普利的抑制作用及机制  

Inhibition of nonenzymatic glycation in renal glomeruli of exprimental diabetes by benazepril

作　　者：黄宇峰[1] 林善锬[1] 

机构地区：[1]上海医科大学华山医院肾脏病科,200040

出　　处：《中华肾脏病杂志》1999年第4期241-244,共4页Chinese Journal of Nephrology

基　　金：国家自然科学基金

摘　　要：目的　探讨苯那普利对糖尿病肾小球内非酶促糖化反应的作用及机制。方法　以链脲佐菌素诱发的单侧肾切除糖尿病大鼠为模型，检测苯那普利投药４ 周后，糖尿病大鼠血胰岛素水平、肾功能指标、血清及肾小球内糖化产物表达水平的改变。结果　用药的糖尿病大鼠，肾功能指标［ Ｂ Ｕ Ｎ 从（１７３８ ±２２２）ｍ ｍｏｌ／ Ｌ 降至（１２８３ ±２０９）ｍ ｍｏｌ／ Ｌ， Ｐ ＜ ００５］ 、血清糖化蛋白水平［ 果糖胺从（５３０３ ±０１２３）ｍｍｏｌ／ Ｌ降至（２００３ ±０１２５）ｍ ｍｏｌ／ Ｌ， Ｐ ＜ ００５］ 明显下降，肾小球外基质（ Ｅ Ｃ Ｍ） 积聚被抑制，非酶糖化反应程度以及晚期糖化产物（ Ａ Ｇ Ｅｓ） 的蓄积亦有明显改善。血浆游离胰岛素水平升高［ 从（９０２ ±２３４） ｍ Ｕ／ Ｌ 升至（１６７ ±７１３）ｍ Ｕ／ Ｌ， Ｐ＜ ００５］ ，因而高血糖程度稍有改善。结论　苯那普利对糖尿病大鼠肾小球内基质蛋白的非酶糖化有显著的抑制作用，其作用途径与其部分改善胰岛功能。Objective To investigate whether benazepril can affect the process of nonenzymatic glycosylation in vivo and to study its mechanism.Methods Uninephrectominzed rats were divided into three groups-control, strepotozotocin induced diabetic rats(DM) with or without benazepril or without treatment and followed up for 4 weeks.Results In untreated diabetic rats, significant increases of blood glucose (BG), BUN and Scr were observed, but the level of serum insulin was markedly reduced[DM vs. control,[9.02±2.34]vs.[32.14±10.02]mU/L , P<0 001].Benazepril ameliorated all those alterations mentioned above.Concentration of Amadori products in plasma examined by nitroblue tetrazolium (NBT) method in untreated diabetic rats was significantly increased [DM vs.control,(5.30±0.12)vs.(0.79±0.14)mmol/L,P<0 001]. Similarly, the intensity of NBT staining in the glomerular mesangial areas and capillary walls was marked in diabetic rats. Furthermore, AGEs was stained significantly in glomeruli in diabetic rats, compared to control rats (AGEs was not detected). DM group was also associated with marked glomerular extracellular matrix accumulation and mesangial expansion (PAS staining). Benazepril administration made all changes restore nearly to normal status. Conclusion Benazepril may inhibit nonenzymatic glycation of proteins, either the early glycation products or AGEs formation in renal glomeruli, which could contribute to retarding effectively the development of renal injury in diabetes.

关 键 词：糖尿病 肾小球 非酶糖化 苯那普利 

分 类 号：R587.1[医药卫生—内分泌] R692[医药卫生—内科学]