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目的研究内质网应激相关因子葡萄糖调节蛋白78(GRP78)和CCAAT/增强子结合蛋白同源蛋白(CHOP)在噪声应激环境高血压大鼠模型心肌中的表达,并探讨GRP78和CHOP变化与高血压及其心肌重构的关系。方法将成年雄性Sprague-Dawly(SD)大鼠40只随机分为两组:噪声组(采用噪声环境建立高血压模型)和对照组(不予任何刺激正常喂养),每组20只。按应激时间不同,噪声组和对照组又分为2、4、6、8周4个亚组,每组5只大鼠。颈动脉插管测定各组大鼠的平均动脉压(MAP)。超声检测室间隔厚度(IVST)、左心室后壁厚度(LVPWT)、射血分数及E/A。称取体质量及左心室质量,计算左心室质量指数(LVMI)。LVMI=左心室质量/体质量。免疫组化法检测大鼠心肌GRP78及CHOP蛋白表达,Western-blot法检测大鼠心肌GRP78及CHOP蛋白含量,TUNNEL法检测心肌细胞凋亡情况。结果①随应激时间延长,噪声组大鼠MAP逐渐升高,均明显高于对照组(P<0.01);②噪声各亚组的IVST、LVPWT及LVMI随时间的延长逐渐增大,其中4、6及8周亚组的IVST较相应对照组分别增大29%、33%及38%,LVPWT分别增大29%、29%及33%,LVMI分别增高23%、30%和26%(P<0.05);噪声组的E/A及射血分数分别从2周及6周起逐渐下降;③随着应激时间的延长,噪声组大鼠心肌GRP78蛋白含量逐渐增高,4周达最高值,此后逐渐下降;CHOP蛋白表达水平逐渐增高,与相应对照组相比较,差异有统计学意义(P<0.01)。噪声组的心肌细胞凋亡率增加。结论噪声应激可以引起心肌细胞内质网应激,导致GRP78和CHOP二者呈不对称性表达,促使心肌细胞凋亡逐渐增加,引起心肌细胞的损害,参与大鼠高血压及心肌重构的过程。
Objective To study the expression of ER stress-related factors glucose regulatory protein 78 (GRP78) and CCAAT / enhancer binding protein (CHOP) in cardiac muscle of noise-stressed environmental hypertensive rats and to explore the changes of GRP78 and CHOP Relationship with Hypertension and Myocardial Remodeling. Methods Forty adult male Sprague-Dawly (SD) rats were randomly divided into two groups: noise group (hypertension model with noisy environment) and control group (n = 20). According to the different stress time, noise group and control group were divided into 2,4,6,8 weeks 4 subgroups, each group of 5 rats. The mean arterial pressure (MAP) of rats in each group was measured by carotid artery cannulation. The thickness of interventricular septum (IVST), left ventricular posterior wall thickness (LVPWT), ejection fraction and E / A were detected by ultrasound. Weigh mass and left ventricular mass and calculate left ventricular mass index (LVMI). LVMI = left ventricular mass / body mass. The expressions of GRP78 and CHOP protein in myocardium of rats were detected by immunohistochemistry, the content of GRP78 and CHOP protein in myocardium were detected by Western-blot, and the apoptosis of cardiomyocytes was detected by TUNNEL. Results ① With the prolongation of stress time, MAP of rats in noise group increased gradually, which were significantly higher than that of control group (P <0.01); ② The IVST, LVPWT and LVMI of noise subgroups gradually increased with time prolonging, among which 4 IVST increased by 29%, 33% and 38%, LVPWT increased by 29%, 29% and 33%, LVMI increased by 23%, 30% and 26% P <0.05). The E / A and ejection fraction of noise group decreased from 2 weeks and 6 weeks respectively. (3) With prolonging of stress time, GRP78 protein in myocardium of noise group increased gradually and reached the highest at 4 weeks (P <0.01). Compared with the corresponding control group, the CHOP protein expression level gradually increased (P <0.01). The rate of apoptosis of cardiomyocytes in noise group increased. Conclusion The noise stress can cause the endoplasmic reticulum stress in cardiomyocytes, resulting in asymmetric expression of both GRP78 and CHOP, leading to the gradual increase of cardiomyocyte apoptosis, causing the damage of cardiomyocytes and participating in the hypertensive and myocardial remodeling of rats process.