自发性高血压大鼠心肌纤维化时序动态变化  

Chronological changes in myocardial fibrosis in spontaneously hypertensive rats

作　　者：赵健清 丁露[2] 曾俊义[1,2] 应国秋[1] 文渊[1] 聂俊刚[1] 易达松 ZHAO Jianqing;DING Lu;ZENG Junyi;YING Guoqiu;WEN Yuan;NIE Jungang;YI Dasong(Department of Cardiology,the First Affiliated Hospital of Nanchang University,Nanchang 330006,China;Jiangxi Hypertension Research Institute,the First Affiliated Hospital of Nanchang University,Nanchang 330006)

机构地区：[1]南昌大学第一附属医院心血管内科,南昌330006 [2]南昌大学第一附属医院高血压病研究所,南昌330006

出　　处：《中国实验动物学报》2021年第6期724-729,共6页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金资助项目(81760082);江西省自然科学基金资助项目(20181BAB205005);江西省教育厅科学技术研究重点资助项目(GJJ170040);江西省卫生健康委科技计划(202130196)。

摘　　要：目的观测自发性高血压大鼠心肌纤维化时序动态变化。方法纳入4周龄SPF级雄性自发性高血压大鼠(spontaneously hypertensive rats,SHR)45只、京都种Wistar大鼠(Wistar Kyoto rats,WKY)35只,随机分笼饲养至42周,分别于预设时点尾套法监测收缩压,超声心动图监测心脏结构与功能;解剖大鼠心脏标本并计算左室质量指数(left ventricular mass index,LVMI),Masson染色观测左室组织纤维化,qRT-PCR检测左室组织纤维化相关基因TGF-β_(1)、Ⅰ型胶原、Ⅲ型胶原。结果6~12周SHR收缩压快速上升,12周时明显高于WKY(P<0.05),此后SHR血压趋于平稳并维持高位。伴随血压及鼠龄变化,SHR左室结构相关指标室间隔厚度(interventricular septal thickness,IVST)、左室后壁厚度(left ventricular posterior wall thickness,LVPWT)、LVMI均呈现特征性动态变化。SHR胶原容积分数(collagen volume fraction,CVF)随鼠龄增长逐渐增加,12周开始即显著高于WKY(P<0.05)。SHR左室心肌纤维化相关基因TGF-β_(1)、Ⅰ型胶原、Ⅲ型胶原表达均呈现随鼠龄增长先降后升变化,且32周后大幅上调。结论SHR心肌纤维化伴随鼠龄及血压变化不断发展演变,并从结构到功能,宏观入微观均呈现出时序动态特征性改变。Objective To study the chronological changes in myocardial fibrosis in spontaneously hypertensive rats. Methods Forty-five male spontaneously hypertensive rats(SHR) and 35 male Wistar Kyoto rats(WKY) that were four weeks old and specific-pathogen-free were randomly selected and fed in cages until 42 weeks. Systolic blood pressure was measured by the tail-cuff method, and cardiac structure and function were detected by echocardiography at pre-set time points. At the same time points, heart specimens were dissected, and the left ventricular mass index(LVMI) was calculated. Myocardial fibrosis of the left ventricle was detected by Masson staining, and TGF-β1, collagen Ⅰ and collagen Ⅲ were detected by qRT-PCR. Results The blood pressure of SHR increased rapidly from 6 weeks to 12 weeks and was significantly higher than that of WKY rats at 12 weeks(P < 0.05) and then stabilized and remained high. With age and blood pressure changes, the structure-related indexes of the left ventricle, including interventricular septal thickness(IVST), left ventricular posterior wall thickness(LVPWT) and LVMI, all showed dynamic characteristic alterations. The collagen volume fraction(CVF) gradually increased with the age of SHR and was significantly higher than that of WKY rats at 12 weeks and later(P< 0.05). The expression of the fibrosis-related factors TGF-β1, type Ⅰ collagen and type Ⅲ collagen in the left ventricle myocardium of SHR all decreased at first and then increased with age to statistically significant levels after 32 weeks. Conclusions With increasing age and blood pressure, myocardial fibrosis in SHR continuously develops and presents with the typical characteristics of chronological changes, including structure, function, macro and micro alterations.

关 键 词：自发性高血压大鼠 心肌纤维化 时序 动态变化 

分 类 号：Q95-33[生物学—动物学]