自发性高血压大鼠心肌细胞凋亡与左心室功能的关系

The relationship between cardiomyocyte apoptosis and left ventricular function in spontaneously hypertensive rats

目的观察自发性高血压大鼠(SHR)增龄过程中心肌细胞凋亡的分布特点和凋亡相关蛋白[B淋巴细胞瘤-2(Bcl-2)、Bax]表达的变化,分析心肌细胞凋亡与左心室结构功能及凋亡相关蛋白的关系。方法购进12周龄雄性SHR 36只、WKY大鼠30只,分笼饲养,分别在14、28、45、66、84、102周应用超声心动图评价左心室质量指数(LVMI)、左心室射血分数(LVEF),组织学观察心内膜下及心外膜下的心肌细胞凋亡情况,Western blot定量检测凋亡相关蛋白Bcl-2、Bax水平。结果 (1)SHR的LVMI随增龄而增加,LVEF在14~66周龄差异无统计学意义,在84~102周龄时出现明显下降;(2)SHR心肌细胞凋亡指数随周龄增加而增加,其中心内膜下心肌细胞凋亡指数(APOI-endo)在66周龄显著增加且高于同周龄WKY组(9.83±3.97比4.03±2.06,P<0.05),而心外膜下心肌细胞凋亡指数(APOI-epi)在84周龄时才出现显著增加(P<0.05);SHR组在66周龄时Bax/Bcl-2明显高于WKY组(3.98±0.80比0.29±0.06,P<0.05),102周龄时更为显著(10.54±1.60比0.70±0.13,P<0.05)。(3)心肌细胞凋亡指数与LVMI呈正相关(r=0.83,P<0.01),与LVEF值在66~102周龄呈负相关(r=-0.81,均P<0.01),与Bax/Bcl-2呈正相关(r=0.79,P<0.01)。结论 SHR增龄过程心肌细胞凋亡的增加与左心室重构及收缩功能不全相关,凋亡相关蛋白Bax/Bcl-2增高与心肌细胞凋亡指数的增加相关。

Objective To investigate the distribution of cardiomyocyte apoptosis and the expression of apoptosis-related proteins[B-cell lymphoma-2(Bcl-2),Bax]in spontaneously hypertensive rats(SHR)during aging.And to further analyze its relationship with the left ventricular structure,function and apoptosis-related proteins.Methods Male SHR(n=36)and Wistar-Kyoto rats(WKY,n=30)aged 12 weeks were purchased and fed in different cages.At 14,28,45,66,84,102 weeks of age,left ventricular mass index(LVMI)and left ventricular ejection fraction(LVEF)were evaluated by echocardiography.The cardiomyocyte apoptosis in subendocardium and subepicardium was analyzed by histology.Then the apoptosis-related proteins(Bcl-2,Bax)were quantitatively detected by Western blot.Results LVMI in SHR increased with age.LVEF showed no significant difference at the age of 14-66 weeks,but it decreased significantly in SHR aged 84-102 weeks.The apoptotic index(APOI)of myocardial cells in SHR increased with age,in which subendocardial APOI(APOI-endo)increased obviously at the age of 66 weeks and was significantly higher than that in age-matched WKY(9.83±3.97 vs 4.03±2.06,P<0.05).Additionally,the subepicardial APOI(APOI-epi)increased significantly at 84 weeks of age(P<0.05).The expression of Bax/Bcl-2 in SHR was higher than that in WKY at the age of 66 weeks(3.98±0.80 vs 0.29±0.06,P<0.05),and aggravated at 102 weeks(10.54±1.60 vs 0.70±0.13,P<0.05).Myocardial APOI was positively correlated with LVMI(r=0.83,P<0.01),negatively with LVEF in 66-102 weeks(r=-0.81,P<0.01),and positively with Bax/Bcl-2(r=0.79,P<0.01).Conclusion The myocardial apoptosis increased with aging and was related with left ventricular remodeling and systolic dysfunction in SHR.Additionally,the cardiac apoptotic index was associated with the increased Bax/Bcl-2 ratio.