小檗碱对压力负荷所致心肌肥厚大鼠的保护作用

目的:通过动物实验探讨小檗碱(Berberine)对压力负荷所致大鼠心肌肥厚模型的保护作用,并探讨其作用机制。方法:通过主动脉缩窄术构建大鼠心肌肥厚模型,将造模成功的16只SD大鼠随机分为模型组及模型+小檗碱组,另外将假结扎主动脉的8只大鼠入组假手术组。术后4周,利用心脏超声测定大鼠的心功能指标;HE、Masson及TUNEL染色等分子生物学方法测定心肌细胞大小、心脏纤维化、心肌细胞凋亡等指标;同时使用RT-q PCR法检测左室心肌组织心房利钠因子(ANP)m RNA的表达;采用Western blot的方法检测内质网应激相关指标Bip/GRP78和CHOP的蛋白表达情况。结果 :与模型组相比,小檗碱可明显改善主动脉缩窄所致的心功能紊乱,显著降低心肌细胞大小(P<0.05)、心脏组织的纤维化程度以及心肌细胞凋亡比率(P<0.05);Western blot结果表明,小檗碱治疗可明显降低长期压力超负荷所致的内质网应激相关指标Bip/GRP78和CHOP的表达的增加(P<0.05)。结论 :小檗碱可显著改善压力超负荷所致的心肌肥厚及心功能紊乱,抑制心肌细胞凋亡,对肥厚型心肌起保护作用,且此种心脏保护性作用可能与其抑制压力负荷所致的内质网应激相关。

Cardioprotective effects and mechanisms of Berberine on pressure overload induced cardiac hypertrophy in rats models

Objective:To investigate the beneficial effects and the potential molecular mechanisms of Berberine on cardiac hypertrophy induced by pressure overload in rats. Methods: Transverse aortic constriction (TAC) surgery was conducted to set cardiac hypertrophy model in rats. There were three groups: the sham group (n=8), the TAC group (n=8),and the TAC + Berberine group (n=8). Echocardiography was performed to evaluate the cardiac function 4 weeks after the TAC surgery. Histopathology staining, Masson trichrome staining, TUNEL staining, and other molecular biology methods were performed to measure myocardial cell size, cardiac fibrosis, myocardium cell apoptosis, and other indexes. The mRNA expression of atrial natriuretic factor (ANP) was detected by RT-qPCR. To evaluate endoplasmic reticulum (ER) stress level, Western blotting was carried out to test the expression of ER stress associated proteins Bip/GRP78 and CHOP. Results: Compared with the TAC group, Berberine significantly improved cardiac hypertrophy situation (P < 0.05), reduced myocardial interstitial fibrosis and cardiac apoptosis (P < 0.05). Western blotting showed that Berberine administration remarkably decreased the expression of Bip/GRP78 and CHOP induced by TAC surgry (P < 0.05). Conclusion: Berberine could protect hypertrophic myocardium by attenuating TAC-induced cardiac hypertrophy and dysfunction and inhibiting myocardial cell apoptosis, and that cardioprotective effect of Berberine is, at least in part, associated with reducing endoplasmic reticulum stress-meditated apoptosis.