拉西地平对内质网应激导致左室重塑的保护作用

目的:研究在高温高湿应激状态下拉西地平对葡萄糖调节蛋白(glucose-regulated protein78,GRP78)和C/EBP环磷酸腺苷反应元件结合转录因子同源蛋白(C/EBP-homologous protein,CHOP)在大鼠心肌中表达及对心室重塑的影响。方法:将30只雄性Sprague-Dawly(SD)大鼠随机分为对照组、高温高湿组、拉西地平干预组,每组10只。喂养6周后颈动脉插管测定平均动脉压及心率。B超检测左室形态结构。免疫组化法检测大鼠心肌GRP78及CHOP蛋白及表达水平。结果:高温高湿组的大鼠平均动脉压(MBP)、隔厚度(IVST)、左室后壁厚度(LPWT)、左室重量指数(LVWI),GRP78及CHOP蛋白表达水平与对照组相比均有显著升高(p<0.01),拉西地平干预组能显著降低大鼠平均动脉压(MBP)、室间隔厚度(IVST)、左室重量指数(LVWI),GRP78及CHOP蛋白的表达水平(p<0.05)。结论:内质网应激可能参与了高温高湿诱导的左室重构;拉西地平可能通过降低GRP78及CHOP的表达干预了ERS介导的心肌肥厚通路,从而改善心脏功能。

Protective effects of Lacidipine against left ventricular remodeling caused by endoplasmic reticulum stress in rats

Objective: To investigate the influence of Lacidipine on the expression of glucose-regulated protein 78 (GRP78) and C/EBP-homologous protein (CHOP) in rat cardiomyocytes and the effects of it against left ventricular remodeling under the high temper ature and humidity conditions. Methods: 30 male SD rats were randomly divided into control group, high temperature and humidity group and high temperature and humidity + Lacidipine group (0.5 mg·kg-1·d-1 per gavage, n=10). 6 weeks later, the MBP and HR were measured through carotid artery incubation, and the morphology of left ventricular was monitored by B- Ultrasound. The expression of GRP78 and CHOP in rat cardiomyocyte were examined by immunohistochemistry. Results: The (mean arterial pressure) MBP, (inter ventricular steptal thickness)IVST,( Left ventricular thick wall thickness)LPWT, (Left entricular mass index)LVWI, as well as the expression of GRP78 and CHOP in cardiomyocyte were remarkably increased in high temperature and humidity group when compared with control group (P<0.01). While Lacidipine could significantly decrease MBP, IVST, PWT, LVWI of the rats and down-regulate the expressions of GRP78 and CHOP in cardiomyocyte (P<0.05). Conclusion: The endoplasmic reticulum stress may be involved in the left ventricular remodeling caused by high temperature and humidity. Lacidipine may exerts an protective effect on heart by inhibiting the endoplasmic retieulum stress via down-regulating the expression of GRP78 and CHOP.