阿托伐他汀对高温高湿应激大鼠心肌细胞GRP78和CHOP表达的影响

探讨阿托伐他汀对高温高湿应激大鼠心肌细胞内内质网应激相关因子葡萄糖调节蛋白78(glucose-regulated proteinof 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。将60只雄性SD大鼠随机分为对照组、高温高湿组、阿托伐他汀组,每组20只。按实验时间(2 w、4 w、6w、8 w)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)。心脏超声心动图检测左心室形态结构。用免疫组织化学法检测心脏GRP78和CHOP的表达水平。①高温高湿各亚组的MAP随着实验时间的延长呈逐渐递增的趋势,高温高湿4 w、6 w、8 w亚组的MAP均高于相应的对照组和阿托伐他汀组(P<0.05)。②高温高湿组心肌细胞中GRP78在2 w即有低水平表达,高于对照组,但无统计学意义。随着实验时间的延长,高温高湿组GRP78表达量不断增加,6 w达到最大值,8 w表达减弱。高温高湿4 w、6 w、8 w亚组GRP78表达量均高于相应对照组和阿托伐他汀组,有统计学意义(P<0.05)。③高温高湿组2 w、4 w、6 w、8 w亚组CHOP表达量组间比较有统计学意义(P<0.05),8 w亚组表达达到最高值。高温高湿组2 w、4 w亚组与相应对照组比较无统计学意义(P>0.05);高温高湿组6 w、8 w亚组与相应对照组和阿托伐他汀组比较有统计学意义(P<0.05)。说明高温高湿应激可引起心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心肌细胞的损害。阿托伐他汀可以减轻内质网应激,逆转高温高湿应激所致的心肌细胞的损伤作用,对心肌细胞有保护作用。

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

To study the effects of Atorvastatin on the expression of GRP78 and CHOP in the myocardial cells of the high temperature and humidity stress rats,sixty sprague-dawley(SD) rats were divided randomly into three groups: the control group(n=20),the high temperature and humiditygroup(n=20) and the Lacidipine group(n=20).And each group included four subgroups: 2 w、4 w、6 w、8 w,and each subgroup had 5 rats.Mean arterial blood pressure(MAP) was measured by carotid artery intubation,and the morphology of left ventricular was monitored by echocardiography.The expression of GRP78 and CHOP in the myocardial cells of each subgroup was detected by immunohistochemistry.It is resulted that: ①Mean arterial blood pressure(MAP) of 4 w、6 w、8 w subgroups in the high temperature and humidity group increased significantly compared with that of the according control group and the according Atorvastatin group(P<0.05).And it increased progressively during the experiment.②Compared with that of the according control group,the expression of GRP78 in the subgroups of 4 w、6 w、8 w in the high temperature and humidity group increased significantly(P<0.05).No significant difference(P>0.05) was observed between OD of 2 w subgroup in the temperature and high humidity group and 2 w subgroup in the control group.And OD of the 6 w subgroup in the model group was the highest.③The expression of CHOP in the subgroups of 6 w,8 w in the high temperature and humidity group increased significantly(P<0.05) compared with that of the according control group and the according Atorvastatin group,and that of the 8 w subgroup in the temperature and high humidity group was the highest.It is conclused that ERS is induced in the myocardial 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 myocardial cell damage.Atorvastatin which can weaken endoplasmic reticulum stress,have a protective effect on myocardial cells.