伊贝沙坦对结缔组织生长因子在自发性高血压大鼠心室肌表达的影响

摘要/Abstract

摘要： 目的: 研究结缔组织生长因子(CTGF)在自发性高血压大鼠(SHR)心脏中的表达及其与高血压心室重构和心肌纤维化的关系,并探讨血管紧张素II受体拮抗剂对其表达的影响以及改善高血压心室重构和心肌纤维可能的作用机制。方法: 20只12周龄雄性自发性高血压大鼠随机分为SHR组(n=10)和伊贝沙坦组(n=10),伊贝沙坦组每只大鼠予以伊贝沙坦50mg·kg^-1·d^-1灌胃,给药12周,同时取10只12周龄雄性京都种Wistar(WKY)大鼠作为对照组,用免疫组化的方法对TGF-β1、CTGF在三组大鼠的左室心肌的分布及表达进行半定量分析;用RT-PCR的方法检测TGF-β1、CTGFmRNA在心肌表达水平;用MASSON染色法观察左室心肌胶原形态,图象分析测量胶原容积分数(CVF)和血管周围胶原面积(PVCA)。结果: (1)左室重量指数(LVI)、CVF、PVCA在SHR组大鼠明显高于WKY组大鼠(P<0.01);相比SHR组,伊贝沙坦组则显著降低(P<0.05)。(2)CTGF主要在血管平滑肌和心肌间质中表达,WKY组在心肌间质中呈弱表达。(3)相关分析表明,CTGF与TGF-β1(r=0.562,P<0.05)的表达呈正相关。(4)CTGF及其mRNA在SHR组左室心肌中的表达较WKY组明显增强(P<0.05),相比SHR组,伊贝沙坦组则明显减少。结论: 高血压大鼠心室肌CTGF表达增加,伊贝沙坦对高血压大鼠心室肌CGTF表达具有抑制作用,且能够明显改善高血压心室重构和心肌纤维化,此种作用可能是血管紧张素II受体拮抗剂抑制左室重构改善心肌纤维化新的机制。

关键词: 结缔组织生长因子, 伊贝沙坦, 自发性高血压大鼠, 心室重构, 心肌纤维化

Abstract: AIM: To investigate the expression of connective tissue growth factor (CTGF) in the myocardium of spontaneously hypertensive rats and the relationship of the hypertensive ventricular remodeling, myocardial fibrosis and whether irbesartan alter this expression.METHODS: 20 twenty-week-old male spontaneously hypertensive rats were randomly assigned to SHR group and irbesartan group (n =10 in each), and 10 twenty-weekold male Wistar Kyoto rats were considered as WKY group.Rats in irbesartan group were given a daily dose of 50 mg·kg^-1 irbesartan for 12 weeks by gavage and the other two groups were fed with a normal diet.TGF-β1 and CTGF were evaluated by qualitative and semiquantitative immunohistochemical staining and semiquantitative reverse transcription polymerase chain reaction.MASSON staining were used in the study of total collagen in left ventricular interstitial tissue.RESULTS: Compared with the WKY group, the left ventricular wight index (LVI), collagen volume fraction (CVF), perivascular collagen area (PVCA) and the expression of TGF-β1, CTGF and its mRNA in left ventricular increased in SHR group (P < 0.05).Compared with the SHR group, these indexes obviously decreased in irbesartan group (P < 0.05).CONCLUSION: Hypertension induces the upregulation of connective tissue growth factor in the myocardium of rat.Treatment with irbesartan, an AngII receptor antagon markedly decreases the enhanced CTGF expression.This may reflect a new mechanism of AngII receptor antagon on preventing left ventricular remodeling and myocardial fibrosis.

Key words: CTGF, spontaneously hypertensive rats, irbesartan, ventricular remodeling, myocardial fibrosis

中图分类号:

R972.4

白玉鹏, 刘昌慧, 杨柳, 刘文举. 伊贝沙坦对结缔组织生长因子在自发性高血压大鼠心室肌表达的影响[J]. 中国临床药理学与治疗学, 2005, 10(8): 947-952.

BAI Yu-peng, LIU Chang hui, YANG Liu. Effects of irbesartan on expression of connective tissue growth factor in myocardium of spontaneously hypertensive rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(8): 947-952.

参考文献

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