拉西地平对高温高湿应激大鼠血管平滑肌细胞GRP78和CHOP表达的影响

Effects of lacidipine on expression of GRP78 and CHOP in vascular smooth muscle cells of rats in high temperature and humidity stress

目的:探讨钙离子拮抗剂拉西地平对高温高湿应激大鼠血管平滑肌细胞内内质网应激相关因子葡萄糖调节蛋白78(glucose-regulated protein of 78kD,GRP78)和C/EBP环磷酸腺苷反应元件结合转录因子同源蛋白(CAAT/enhancer binding protein homologous protein,CHOP)表达的影响。方法:将60只雄性SD大鼠随机分为对照组、高温高湿组、拉西地平组,每组20只。按实验时间(2w、4w、6w、8w)的不同,各组又分为4个亚组,每个亚组5只大鼠。用颈动脉插管法测定各组大鼠的平均动脉压(MAP);用免疫组织化学法检测GRP78和CHOP的表达水平。结果:①高温高湿各组的MAP随着实验时间的延长呈逐渐递增的趋势,高温高湿4w、6w、8w亚组的MAP均显著高于相应的对照组和拉西地平组(P<0.05)。②随着实验时间的延长,高温高湿组GRP78表达量不断增加,6w达到最大值,8w表达减弱。高温高湿4w、6w、8w亚组GRP78表达量均高于相应对照组和拉西地平组,有显著性差异(P<0.05)。③高温高湿组2w、4w、6w、8w亚组CHOP表达量组间比较有显著性差异(P<0.05),8w亚组表达达到最高值;高温高湿组6w、8w亚组与相应对照组和拉西地平组比较有显著性差异(P<0.05)。结论:高温高湿应激可引起血管平滑肌细胞内质网应激反应,导致GRP78表达及CHOP表达的不对称增加,提示高温高湿应激可引起血管平滑肌细胞的损害;拉西地平可以减轻内质网应激,逆转高温高湿应激所致的血管平滑肌细胞的损伤作用,对血管平滑肌细胞有保护作用。

Objective：To study the effects of Lacidipine on the expression of GRP78 and CHOP in the vascular smooth muscle cells of the high temperature and humidity stress rats.Methods：Sixty Sprague-Dawley（SD） rats were divided randomly into three groups：control group（n=20）,high temperature and humidity group（n=20） and Lacidipine group（n=20）.And each group included four subgroups：2w,4w,6w,8w,and each subgroup had 5 rats.Mean arterial blood pressure（MAP） was measured by carotid artery intubation.The ex-pression of GRP78 and CHOP in the vascular smooth muscle cells was detected by immunohistochemistry.Results：①Mean arterial blood pressure（MAP） of 4w、6w、8w subgroups in the high temperature and humidity group increased significantly compared with that of the according control group and the according Lacidipine group（P0.05）.And it increased progressively during the experiment.②Compared with that of the according control group,the expression of GRP78 in the subgroups of 4w,6w,8w in the high temperature and humidity group increased significantly（P0.05）.And OD of the 6w subgroup in the model group was the highest.③The expression of CHOP in the subgroups of 6w,8w in the high temperature and humidity group increased significantly（P0.05） compared with that of the according control group and the according Lacidipine group,and that of the 8w subgroup in the temperature and high humidity group was the highest.Conclusions：ERS is induced in the vascular smooth muscle cells of high temperature and humidity stress rats,which leads to the expression of GRP78 and CHOP increased in mismatch.This means that the high temperature and humidity stress may cause vascular smooth muscle cell damage.Lacidipine which can weaken endoplasmic reticulum stress,has a protective effect on vascular smooth muscle cells.