阻断肾素-血管紧张素系统对糖尿病大鼠肾脏血管紧张素ⅡAT1受体的影响-东南大学学报医学版

阻断肾素-血管紧张素系统对糖尿病大鼠肾脏血管紧张素ⅡAT1受体的影响

单位：1.南京医科大学第一附属医院,肾内科,江苏,南京,210029； 2.复旦大学附属华山医院,肾内科,上海,200040

分类号：R587.1

出版年·卷·期（页码）：2005·24·第六期（380-384）

摘要：

目的:研究链脲佐菌素(STZ)诱导的早期糖尿病大鼠肾组织血管紧张素Ⅱ(AngⅡ)AT1受体的表达以及阻断肾素-血管紧张素系统(RAS)对其的影响.方法:糖尿病模型大鼠随机分为伊贝沙坦组、福辛普利组、两药合用组及糖尿病对照组,另设一正常对照组.采用放射免疫法检测各组血浆AngⅡ水平,免疫组织化学法及Western blot方法半定量检测肾组织中AT1受体的分布和表达.结果:糖尿病大鼠肾组织AT1受体表达较正常大鼠明显减弱,各用药组AT1受体表达较正常对照组明显上调.结论:糖尿病时肾脏局部RAS存在活性改变和重新分布.

Objective To investigate the expression of angiotensin Ⅱ(AngⅡ) type 1(AT1) receptors in the kidney of diabetic rats and its effects of blocking renin-angiotensin system(RAS).Methods Diabetic rats were given angiotensin Ⅱ receptor blocker,irbesartan(40?mg·kg^{-1}),angiotensin-converting enzyme inhibitor,fosinopril(40?mg·kg^{-1}),and irbesartan plus fosinopril(20?mg·kg^{-1},respectively),or placebo per day for 4 weeks.The expression of renal AT1 receptors were assessed by immunohistochemistry and Western blot.Results Immunoblot for AT1 receptors showed that the expression of AT1 receptors decreased significantly in diabetic kidney.Treatment with irbesartan,fosinopril and their combination significantly increased the expression of AT1 receptors compared with that of controls(P<0.05).Conclusion In diabetes mellitus,treatment with irbesartan,fosinopril and their combination changes the expression of AT1 receptors in renal cortex,suggesting that local RAS in diabetic kidney be actively involved in the pathogenesis of DN.

参考文献：

[1] KENNEFICK T M, ANDERSON S. Role of angiotensin Ⅱ in diabetic nephropathy, 1997
[2] TAAL M W, BRENNER B M. Renoprotective benefits of RAS inhibition:from ACEI to angiotensin Ⅱ antagonists. 2000(5). doi:10.1046/j.1523-1755.2000.00031.x
[3] LUCIUS R, GALLINAT S, BUSCHE S. Beyond blood pressure:new roles for angiotensin Ⅱ. 1999(11/12). doi:10.1007/s000180050490
[4] PERICO N, AMUCHASTEGUI S C, COLOSIO V. Evidence that an angiotensin-converting enzyme inhibitor has a different effect in glomerular injury according to the different phase of the disease at which the treatment is started, 1994
[5] ANDERSON S, JUNG F F, INGELFINGER J R. Renin-angiotensin system in diabetic rats:functional,immunohischemical,and molecular biologic correlations, 1993
[6] HSUEH W A, ANDERSON P W. Systemic hypertension and the renin-angiotensin system in diabetic vascular complications, 1993
[7] KIKKAWA R, KITAMURA E, FUJIWARA Y. Biphrasic alteration of renin-angiotensin-aldosterone system in streptozotocin-diabetic rats, 1986
[8] CHENG H F, BECKER B N, BURNS K D. Angiotensin Ⅱ upregulates type-1 angiotensin Ⅱ receptors in renal proximal tubule, 1995
[9] CAMPBELL D J, KLADIS A, VALENTIJN A J. Effects of losartan on angiotensin and bradykinin peptides and angiotensin-converting enzyme, 1995
[10] URATA H, STROBE L, GANTEN D. Wide spread tissue distribution of human chymase, 1994(9)

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录