血管紧张素转化酶抑制剂改善糖尿病大鼠心肌间质重构的类效应研究

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (1): 62-66.

血管紧张素转化酶抑制剂改善糖尿病大鼠心肌间质重构的类效应研究

廖梅梅¹, 熊世熙², 肖然², 闵新文¹, 杨汉东¹

¹郧阳医学院附属东风总医院内一科, 十堰 442008, 湖北;
²武汉大学中南医院心内科, 武汉 430071, 湖北

收稿日期:2008-04-14 修回日期:2008-11-13 出版日期:2009-01-26 发布日期:2020-10-27
通讯作者: 熊世熙,男, 副教授, 主任医师, 硕士生导师, 研究方向:心肌保护, 代谢综合症。Tel:13607192875 E-mail:xiongshixi@126.com
作者简介:廖梅梅, 女, 硕士, 住院医师, 研究方向:心肌保护。Tel:13627236726 　E-mail:chenliaomeimei@163.com
基金资助:
湖北省卫生厅重点研究项目(JX2A19)

Class effect of ACEI in improving myocardial interstitial remodeling of diabetic rat

LIAO Mei-mei¹, XIONG Shi-xi², XIAO Ran², MING Xin-wen¹, YANG Han-dong¹

¹Dongfeng General Hospital of Yunyang Medical College, Shiyan 442008, Hubei, China;
²Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China

Received:2008-04-14 Revised:2008-11-13 Online:2009-01-26 Published:2020-10-27

摘要/Abstract

摘要： 目的: 通过4 种血管紧张素转化酶抑制剂(ACEI) 类药物对糖尿病大鼠心脏指数、心肌胶原含量及转化生长因子(TGF-β₁ ) 、基质金属蛋白酶及其抑制剂(MMP-1, TIMP-1) 表达的影响, 籍以了解不同ACEI 药物减轻糖尿病大鼠心肌间质重构有无类效应。方法: 50 只SD 大鼠用链脲佐菌素(STZ) 注射制备糖尿病模型, 成功后随机分为模型组(n=9) 、咪达普利组(10 mg/kg, n=9) 、卡托普利组(50 mg/kg, n=9) 、贝那普利组(10 mg/kg, n=9) 、福辛普利组(5 mg/kg, n=10), 另取10 只正常鼠作为正常对照组。免疫组化法测Ⅰ 型胶原、Ⅲ型胶原、TGF-β₁ 、TIMP-1 和MMP-1 蛋白的表达,RT-PCR 法测TIMP-1 和MMP-1 mRNA 的表达。结果: 模型组心脏指数和左心室指数显著高于正常对照组(P<0.05), Ⅰ 型胶原、Ⅲ型胶原的表达也增加, 存在着心肌间质重构, TGF-β1 、TIMP-1 蛋白及TIMP-1 mRNA 表达增高, MMP-1 蛋白及MMP-1mRNA 表达减少。使用ACEI 药物后, 各项指标均有所改善, 卡托普利某些指标与其余3 组之间存在统计学差异(P<0.05) 。结论: 四种ACEI 类药物都可通过减少TGF-β₁ 、TIMP-1 的表达而增加MMP-1 的表达而改善糖尿病心肌间质的重构, 具有类效应, 作用效果与对血管紧张素Ⅱ(Ang Ⅱ) 的不同影响有关。

关键词: 心肌间质重构, 类效应, 血管紧张素转化酶抑制剂

Abstract: AIM: Through comparing 4 ACEIs'influence in cardiac index, expression levels of typeⅠ, type III collagen, TGF-β₁, MMP-1 and TIMP-1 of diabetic rats to investigate the class effect of the ACEIs in improving myocardial interstitial remodeling of diabetic rat.METHODS: 50 male SD rats were injected streptozotocin(STZ) to induce into diabetic mellitus(DM), then the rats were divided into model group(n=9), captopril treated group (50 mg/kg, n=9), imidapril treated group(10 mg/kg, n=9), benazepril treated group(10 mg/kg, n=9) and fosinopril treated group (5 mg/kg, n=10).10 male SD rats were choosed as normal control group.Immunohistochemistry was used to measure the expression levels of type Ⅰ, type Ⅲ collagen, transforming growth factor beta 1(TGF-β₁ ) protein, matrix metalloproteinases (MMP)-1 and tissue inhibitors of metalloproteinases (TIMP)-1 protein.The mRNA of MMP-1 and TIMP-1 mRNA were measured by RT-PCR.RESULTS: By the end of the experiment, the cardiac index and the ventricle index were significantly higher in the model group than those in the normal control group (P<0.05).The expression of type I, type III collagen, TGF-β1 protein, TIMP-1 protein and mRNA were also significantly higher than in the normal control group while the expression of MMP-1 protein and mRNA were significantly lower. All the index was greatly improved in the treated groups compared with the model group. There were some difference exist in captopril among other three groups.CONCLUSION: Through increasing the expression of TGF-β₁ and TIMP-1, at the same time decreasing the expression of MMP-1, all the ACEIs could improve the myocardial interstitial remodeling, and the result was effected by the contribution to Ang Ⅱ.

Key words: myocardial interstitial remodeling, class effect, angiotensin-converting enzyme inhibitor

中图分类号:

R965.2

廖梅梅, 熊世熙, 肖然, 闵新文, 杨汉东. 血管紧张素转化酶抑制剂改善糖尿病大鼠心肌间质重构的类效应研究[J]. 中国临床药理学与治疗学, 2009, 14(1): 62-66.

LIAO Mei-mei, XIONG Shi-xi, XIAO Ran, MING Xin-wen, YANG Han-dong. Class effect of ACEI in improving myocardial interstitial remodeling of diabetic rat[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(1): 62-66.

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