自发性高血压大鼠TGF β_1/Smad7通路与心室纤维化的关系  

Exploration of Relationship between TGF β_1/ Smad7 Signaling Pathway and Ventricular Fibrosis in Spontaneously Hypertensive Rats

作　　者：高修仁[1] 翟原生[1] 彭龙云[1] 何旭瑜[1] 郭小刚[1] 朱莺莺[1] 

机构地区：[1]中山大学附属第一医院心内科,广东广州510080

出　　处：《中山大学学报（医学科学版）》2008年第2期163-167,共5页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省自然科学基金资助项目(4009437)

摘　　要：【目的】探讨自发性高血压大鼠心室纤维化过程中TGFβ1和其下游分子Smad7蛋白的表达规律。【方法】雄性自发性高血压大鼠(SHR)14只随机分为2组,SHR22周龄组和SHR14周龄组,另14只WKY大鼠也分为WKY大鼠22周龄组和WKY大鼠14周龄组。在实验动物14周龄和22周龄时,分别测定血压、心室质量指数;以氯胺T法测定心肌羟脯氨酸的含量,免疫组化测定Ⅰ型和Ⅲ型胶原在心肌组织中的表达水平;RT-PCR和Western-blot测定心肌中TGFβ1和其下游分子Smad7的表达。【结果】自发性高血压大鼠在14周龄和22周龄时收缩压都显著高于同龄的WKY大鼠(P<0.001),同时22周龄SHR的收缩压也比14周龄明显升高(P<0.001)。与SHR14周龄组相比,SHR22周龄组的心室质量指数、心肌羟脯氨酸的含量、Ⅰ型和Ⅲ型胶原均明显增加(P<0.01);在mRNA水平或蛋白水平,心肌中的TGFβ1的表达上调,Smad7的表达下调。【结论】在一定的时间窗内,自发性高血压大鼠血压的升高及心肌纤维化随着病程的进展而发展,同时伴随着TGFβ1的表达上调,Smad7的表达下调。[Objective] To explore the correlation between TGFβ1/ Smad7 signaling and ventricular fibrosis in spontaneously hypertensive rats （SHRs）. [Methods] Fourteen male SHRs and 14 Wister Kyoto （WKY） rats matched with the same age and sex, were divided into 2 groups respectively according to the aging of 14 weeks as well as 22 weeks. Tail-cuff pressure was investigated before and at the end of the test, and the left ventricular mass index （LVMI） was measured after autopsy of the animals. Collagen type I, type Ⅲ as well as hydroxyproline contents which reflect myocardial fibrosis was determined by using immunohistochemical analysis. RT-PCR and Western-blot were performed to detect the expression of TGF-1 and Smad7 in the heart. [Results] 14-weeks or 22-weeks SHRs showed significantly higher blood pressure than those of WKY rats matched with age （P 〈 0.001）. 22-weeks SHRs appeared higher blood pressure than that of 14-weeks SHRs （P 〈 0.001）. There were significantly higher LVMI, hydroxyproline contents, Collagen type I and Ⅲ along with up-expression of TGF-1 and down-expression of Smad7 in 22-weeks SHRs comparing with 14-weeks SHRs. [Conclusion] In terms of myocardial fibrosis, there are high blood pressure, rich collagen type I , type Ⅲ, hydroxyproline contents with up-expression of TGF-1 and down- expression of Smad7 during the development of heart remodeling in SHRs.

关 键 词：心室纤维化 TGFΒ1 SMAD7 自发性高血压大鼠 

分 类 号：R363[医药卫生—病理学]