依那普利治疗SHR糖尿病大鼠对肾小球抗氧化酶及肾功能的影响  

Effect of Enalapril on glomerular antioxidant enzymes and renal function in spontaneous hypertensive ratswith diabetes

作　　者：唐政[1] 季大玺[1] 黎磊石[1] 福井光峰[2] 富野康日已 

机构地区：[1]南京大学医学院临床学,210002 [2]日本东京顺天堂大学医学部肾脏科

出　　处：《中华内分泌代谢杂志》1998年第2期119-122,共4页Chinese Journal of Endocrinology and Metabolism

摘　　要：目的　研究依那普利（ Ｅｎａｌａｐｒｉｌ） 治疗自发性高血压（ Ｓ Ｈ Ｒ） 糖尿病（ Ｄ Ｍ） 大鼠对肾功能及肾组织内在抗氧化酶活性的影响，以及肾组织内在抗氧化酶（ Ａ Ｏ Ｅｓ） 在糖尿病高血压状态及糖尿病肾病发病机理中的作用。方法　建立自发性高血压大鼠链脲菌素（ Ｓ Ｔ Ｚ） 诱导的糖尿病动物模型（ Ｓ Ｈ Ｒ＋ Ｄ Ｍ） ，设立依那普利治疗组，常规三联降压组（ 利血平＋ 肼苯哒嗪＋ 双氢克尿噻） ，未治疗组及正常对照组。测定４ 周及１６ 周时肾功能包括尿白蛋白排泄量、肌酐清除率（ Ｃ Ｃｒ） 以及肾小球面积和肾小球内 Ａ Ｏ Ｅｓ包括超氧岐化酶（ Ｓ Ｏ Ｄ） 、谷胱甘肽过氧化酶（ Ｇ Ｓ Ｈ Ｐｘ） 和过氧化氢酶（ Ｃａｔ） 。结果　与正常血压 Ｗ Ｋ Ｙ 大鼠比较，４ 周及１６周的早期糖尿病 Ｓ Ｈ Ｒ 大鼠即已存在肾功能变化， Ｓ Ｈ Ｒ＋ Ｄ Ｍ 大鼠在高血压状态下存在肾组织内在抗氧化酶功能的不全，依那普利及常规三联降压治疗既能使 Ｓ Ｈ Ｒ＋ Ｄ Ｍ 大鼠的血压降至正常，又可使肾功能及肾组织抗氧化酶得于改善，而前者作用明显优于后者。结论　本研究提示抗高血压治疗有益于糖尿病大鼠肾组织内在抗氧化酶及肾功能，肾组织内在 Ａ Ｏ Ｅｓ 的缺乏及高血压可能都在?Objective To study the effects of Enalapril on renal function and intrinsic glomerular antioxidantenzymes ( A O Es) in diabetic rats with hypertensive state and the pathogenic role the A O Es play in the developmentof diabetic nephropathy . Methods The rats were randomly divided into five groups ,that is, Wistar Kyoto rats( W K Y, n = 8) as normotensive control, spontaneous hypertensive rats ( S H R,n = 8) as hypertensive control, S H Rdiabetes ( S H R+ D M, n = 8) induced by streptozotocin ( S T Z) , S H R+ D Mtreated with Enalapril ( S H R+ D M+ E, n = 8) ,and S H R+ D M treated with triple antihypertensive therapy ( S H R+ D M+ T, n = 8) . Theglomerular activities of S O D, G S H Px and catalase as well as urinary albumin excretion ( U A E) ,renal function( C Cr) and glom erular area were determined in S T Ztreated S H Rat 4th and 16th weeks. Results In S H R+ D M, urinary albu min excretion , creatinine clearance and glo merular area significantly increased with age ,however,the intrinsic glomerular A O Es markedly decreased as co mpared with those in W K Yand S H Rboth at 4thand 16th week . These abnormalities were ameliorated by both antihypertensive therapies ,but being more effective in S H R+ D M + Ethan in S H R + D M + T. As co mpared with S H R+ D M, S H R had higher S O Dand G S H Pxactivities as well aslower C Cr and U A Evalues . Moreover ,glomerular area and U A Em arkedly increased in S H R+ D Mas compared with those in W K Y. Conclusion Our study suggests :1) Overproduction ofreactive oxygen species( R O S) beyond the cell to eliminate , and the insufficiency of A O Es and hypertensive state may contribute to thedevelopment of diabetic nephropathy in diabetic S H R. 2) Both Enalapril and triple antihypertensive therapy canimprove renalfunction and intrinsic glomerular A O Es in S H R with diabetes.

关 键 词：肾功能 SHR 肾组织 治疗 依那普利 糖尿病大鼠 抗氧化酶 过氧化氢酶(Cat) 岐化酶 缺乏 

分 类 号：R587[医药卫生—内分泌] R544[医药卫生—内科学]