适应性心肌肥大机制中热休克蛋白及其转录因子1的正向调控作用

Protective effect of heat shock transcription factor （HSF1） in adaptive cardiac hypertrophy of mice

目的 探讨热休克蛋白（Hsp）及其转录因子1（HSF1）在运动性心脏肥大小鼠心肌中的表达及对心肌的保护作用.方法 取8周龄雄性同窝野生型小鼠48只,其中24只转入人HSF1基因.将转基因小鼠与野生型分别随机分为3组：假手术模型组（对照组）、运动诱导心肌肥大模型组（运动诱导组）、高血压诱导心肌肥大模型组（高血压诱导组）.运动诱导模型制作：给予5周的运动锻炼 高血压诱导模型制作：结扎小鼠腹主动脉5周.5周后对3组小鼠进行心脏超声检测,同时对心肌组织进行组织学分析以及Hsp70、Hsp27和HSF1的检测.结果 与对照组比较,高血压诱导组心壁厚度明显增大、缩短分数明显降低（均P＜0.05） 与高血压诱导组比较,运动诱导组心率、收缩压及左室舒张末期内径均明显减小（均P＜0.05） 转基因小鼠的2个诱导组心壁厚度均明显小于野生型小鼠（均P＜0.05）,缩短分数均大于野生型小鼠（均P＜0.05）.高血压诱导组及运动诱导组小鼠心肌细胞直径均明显大于对照组（均P＜0.05）,而高血压诱导组小鼠心肌纤维化程度均明显强于运动诱导组及对照组（均P＜0.05） 转基因小鼠2个诱导组心肌细胞直径均明显小于野生型小鼠（均P＜0.05）.运动组小鼠心肌Hsp70和Hsp27的表达显著增强,HSF1的表达也被激发 而且其Hsp70和HSF1的表达较之高血压组和对照组均明显增加 转基因小鼠心肌Hsp70和HSF1的表达较之野生型小鼠增加更明显.结论 HSF1在适应性心肌肥大以及良性与非良性肥大转变中发挥着重要的调控作用,对心脏有着生理性保护作用.

Objective To investigate the effect of heat shock transcription factor 1 （HSF1） in cardiac hypertrophy of mice. Methods Forty eight male brood wild type mice aged 8 weeks were divided into two groups： 24 mice were transferred with human HSF1 gene and the remaining 24 were not. Each groups were randomized into 3 subgroups： sham operation group （control group）, exercise group and hypertension group with 8 mice in each. The hypertension was induced by ligation of abdominal aorta, and mice in exercise group had 5 weeks of exercise. The mice were sacrificed 5 weeks after operation to examine hemodynamic parameters, body weight （BW）,left ventricular weight （LVW） by echocardiography. The morphology of cardiomyocytes was examined by histology analysis, the expressions of Hsp70, Hsp27 and HSF1 were measured by Northern blot and Western blot. Results Cardiac hypertrophy in the hypertension and exercise group was more prominent than that in control group. Fractional shortening （FS） was also significantly decreased than that in control group. The cardiac fibrosis also more marked in the hypertension group. The histology analyses showed that the diameter of cardiomyocytes was larger in the two experimental groups. Expression of HSF1 and heat shock proteins was significantly upregulated in the heart by exercise but not by chronic pressure overload. There were significant differences in the thickness of ventricular wall, FS, the diameter of cardiomyocytes and expression of Hsp70 and HSF1 between wild type groups and HSF1 gene-transferred group. Conclusion HSF1 may have protective effect in progress of cardiac hypertrophy.