高血压诱导大鼠心肌肥大过程中Caspase募集域的凋亡抑制蛋白表达水平的变化  

Caspase recruitment domain expression during the formation of myocardial hypertrophy induced by hypertension in rats

作　　者：万帝[1] 钱令嘉[2] 王新兴[2] 梅竹松[2] 刘伟丽[2] 袁聚祥[1] 

机构地区：[1]河北联合大学公共卫生学院,唐山063000 [2]军事医学科学院卫生学环境医学研究所

出　　处：《中国心血管杂志》2011年第6期443-446,共4页Chinese Journal of Cardiovascular Medicine

基　　金：国家自然科学基金重点项目(30770843);天津市自然科学基金(10JCZDJC19300)

摘　　要：目的探讨高血压致心肌肥大发生发展过程中Caspase募集域的凋亡抑制蛋白(ARC)表达的变化规律。方法选取Wistar大鼠45只,按随机数字表法分为腹主动脉缩窄组、假手术组、对照组(每组15只),腹主动脉缩窄组用腹主动脉缩窄的方法建立高血压心肌肥大模型,每组又按术后1、2、3、4、6周时段平均分为5个亚组。并在心肌肥大形成的不同阶段提取组织蛋白,采用免疫沉淀法检测心肌中ARC的表达水平及其磷酸化状态。结果与假手术组相比,腹主动脉缩窄组血压、左心系数在术后第4周明显升高,病理学结果显示在术后第4周肌纤维增粗,心肌细胞肥大。由Western blot和灰度值分析结果可以看出,在心肌肥大过程中未见ARC表达水平有明显变化,而ARC磷酸化水平在术后第4周明显降低,与假手术组和对照组相比,ARC表达水平差异无统计学意义(P>0.05),第4周和第6周ARC的磷酸化水平差异有统计学意义(P<0.05),对照组与假手术组之间ARC磷酸化水平差异无统计学意义(P>0.05)。结论 ARC磷酸化水平的明显降低可能是导致高血压致心肌细胞肥大的重要分子基础之一。Objective To explore the expression of apoptosis repressor with a caspase recruitment domain （ARC） protein in the development of myocardial hypertrophy in rats. Methods A total of 45 adult healthy Wistar rats were randomly divided into operation group, sham operation group and control group （n = 15 for each group）. Myocardial hypertrophy model was established by using abdominal aortic constriction handing method in operation group. Heart rate, weight ratio of left ventricle to body （LVW/BW）, carotid artery mean arterial blood pressure, and histomorphology of myocardium were compared among three groups after 1, 2, 3,4 and 6 weeks. Expression of ARC and phosphorylated ARC were detected by Western blot and co-immunoprecipitation method. Results Blood pressure and LVW/BW in operation group were increased significantly compared with those in sham operation group after 4 weeks. Myocardial fiber thickening and cardiomyocyte hypertrophy were observed in operation group. The content of ARC in myocardium had no significant change during the formation of myocardial hypertrophy. Expression of phosphorylated ARC was decreased significantly after 4 and 6 weeks in operation group compared with sham group and control group （ both P 〈 0. 05 ）. Conclusions Phosphorylated ARC expression decrease may be one of the important molecular mechanism of myocardial hypertrophy induced by hypertension in rats.

关 键 词：高血压 心肌肥大 Caspase募集域的凋亡抑制蛋白 磷酸化 

分 类 号：R541.3[医药卫生—心血管疾病]