›› 2009, Vol. 8 ›› Issue (1): 43-45.

• 基础研究 • 上一篇    下一篇

莫索尼定及贝那普利对肾组织细胞外基质调节因子影响的研究

邹春波 解汝娟 隋满姝 穆素红 李 丽   

  1. 哈尔滨医科大学附属第一医院肾内科
  • 收稿日期:2008-04-08 修回日期:1900-01-01 出版日期:2009-01-12 发布日期:2009-01-12

A comparison study about the effect of Moxonidine and Benazepril on extracellular maxtrix regulatory factors in rat kidney

ZOU Chun-bo, XIE Ru-juan, SUI Man-shu, MU Su-hong, LI Li   

  • Received:2008-04-08 Revised:1900-01-01 Online:2009-01-12 Published:2009-01-12

摘要: 【摘要】 目的 应用交感神经抑制剂莫索尼定及贝那普利干预阿霉素肾病大鼠,比较二者对肾组织细胞外基质及其调节因子基质金属蛋白酶-9(MMP-9)、基质金属蛋白组织抑制因子-1(TIMP-1)的影响。方法 大鼠右肾摘除加尾静脉注射阿霉素,随机分为模型组、莫索尼定组、贝那普利组、对照组。12周测血、尿生化指标及血压; 光镜及电镜观察肾组织形态学改变;免疫组化检测肾组织MMP-9、TIMP-1蛋白表达;原位杂交测MMP-9mRNA、TIMP-1mRNA表达。结果 与对照组比较,模型组大鼠蛋白尿、血浆NE、AngⅡ水平、血压、肾损害指标均上升;肾组织内MMP-9、TIMP-1蛋白及mRNA表达均明显上调;两治疗组与模型组比较,MMP-9蛋白及mRNA进一步上调,生化指标及TIMP-1都被显著抑制。贝那普利较莫索尼定更明显降低蛋白尿及血浆AngⅡ水平。结论 莫索尼定及贝那普利均具有肾保护作用,部分机制可能是通过抑制交感神经活性,调节细胞外基质降解而起作用。

关键词: 莫索尼定, 贝那普利, 细胞外基质, 基质金属蛋白酶-9, 基质金属蛋白酶组织抑制因子-1

Abstract: 【Abstract】 Objective To compare the effects of Moxonidine and Benazepril on the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in kidney of Adriamycin-treated rats. Method Uninephrectomized Wistar rats were given intravenously Adriamycin and then divided into model group, Moxonidine group (1.5mg/kg), Benazepril group (10mg/kg) and control group. By the end of the 12th week, blood pressure, proteinuria, plasma norepinephrine (NE) and plasma angiotensin II (Ang II) were measured. Kidney pathology was investigated by quantitative histology. MMP-9 and TIMP-1 were determined by immunohistochemical staining. MMP-9 and TIMP-1 mRNAs were evaluated by in situ hybridization. Result In the model group, urinary albumin excretion, plasma NE and Ang II, mean arterial pressure, relative area of interstitial fibrosis, mean glomerular volume, and ratio of kidney weight/body weight were significantly increased, as compared with those of the control group. In the model group, MMP-9 and TIMP-1 and their mRNAs were significantly up-regulated. In the Moxonidine and Benazepril groups, proteinuria, plasma NE and Ang II, and TIMP-1 and its mRNA were significantly down-regulated, but MMP-9 and its mRNA were up-regulated further. Conclusion Moxonidine and Benazepril protect the kidney possibly by inhibiting sympathetic activity and regulating the catabolism of extracellular matrices.

Key words: Benazepril, MMP-9, TIMP-1