压力-应激对大鼠心肌细胞Cx43蛋白表达及心肌纤维化的影响

目的:探讨压力-应激对大鼠心肌细胞间隙连接蛋白-43(Cx43)蛋白表达及心肌纤维化的影响。方法:将20只雄性SD大鼠随机分为正常对照组(n=10)和模型组(n=10),对照组正常饲养,模型组给予不可预测性复合应激结合孤养建立压力-应激大鼠模型。监测两组大鼠的体重变化,并通过组织形态学方法,探讨压力-应激对大鼠心肌细胞Cx43蛋白表达及心肌纤维化的影响。结果:在为期42天的造模过程中,从应激第7天开始,模型组大鼠体重明显低于对照组,差异有统计学意义(P<0.001)。且模型组体重增长缓慢,体重增长百分比明显低于对照组,差异有统计学意义(P<0.001)。与对照组相比,模型组大鼠组织HE染色可见心肌细胞排列紊乱,横纹消失,细胞间隙增大,部分肌纤维断裂、溶解,Masson染色可见心肌间质纤维化,胶原纤维增生、排列紊乱。心肌细胞免疫组化染色可见模型组Cx43蛋白表达明显下降(平均光密度值为0.0110±0.0028),与对照组相比(平均光密度值为0.0268±0.0025),差异具有统计学意义(t=-13.081,P<0.001)。结论:过度疲劳导致猝死的发生可能与Cx43蛋白表达水平的下降引起的恶性心律失常有关。

Effects of Pressure-stress on the Expression of Cx43 Protein and Myocardial Fibrosis in Rat Cardiomyocytes

ABSTRACT Objective: To investigate the effect of pressure-stress on the expression of Connexin-43(Cx43) protein and myocardial fibrosis in rat cardiomyocytes. Methods: 20 male SD rats were randomly divided into normal control group(n=10) and model group (n=10). The control group was fed normally, while the model group was given unpredictable compound stress combined with solitary rearing to establish the pressure-stress rat model. The changes of body weight of rats in the two groups were monitored, and to investigate the effect of pressure-stress on the expression of Cx43 protein and myocardial fibrosis in rat cardiomyocytes by histomorphology. Results: During the 42 days modeling process, the weight of rats in the model group was significantly lower than that in the control group from the 7th day(P<0.001). The weight gain of model group was slow and the percentage of weight gain was significantly lower than that of control group(P<0.001). Compared with the control group, HE staining showed disordered arrangement of myocardial cells, disappearance of transverse striations, enlargement of intercellular space, breakage and dissolution of some muscle fibers in the model group. Masson staining showed myocardial interstitial fibrosis, proliferation and disordered arrangement of collagen fibers. Immunohistochemical staining of myocardial cells showed that the expression of Cx43 protein in the model group was significantly decreased (average optical density was 0.0110±0.0028), compared with the control group (average optical density was 0.0268±0.0025), the difference was statistically significant (t=-13.081, P<0.001). Conclusion: Sudden death caused by overwork may be related to malignant arrhythmia caused by decreased expression of Cx43 protein.