噪声应激对大鼠心肌葡萄糖调节蛋白78和CCAAT/增强子结合蛋白同源蛋白表达的影响与高血压及心肌重构的关系  

Effect of noise stress on the expression of myocardial glucose-regulated protein 78 and C/EBP-homologous protein and its relationships with myocardial remodeling in rats

作　　者：胡中伟[1] 赵连友[1] 刘沙沙[1] 尚福军[1] 艾永飞[1] 槐勇[1] 李炜[1] 

机构地区：[1]第四军医大学唐都医院心血管内科,陕西西安710038

出　　处：《中华高血压杂志》2011年第9期836-841,共6页Chinese Journal of Hypertension

基　　金：军队"十一五"重要军事医学基础研究项目资助(062074)

摘　　要：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 glucose-regulated protein 78（GRP78） and C/EBP-homologous protein（CHOP） in myocardial cells in rat noise-induced stress model and explore the relationship between these changes and the myocardial remodeling.Methods Forty male SD rats were divided randomly into two groups： the noise group（n=20）,the control group（n=20）.According to the different exposure time,the noise group was further divided into 4 groups： 2 weeks noise（n=5）,4 weeks noise（n=5）,6 weeks noise（n=5） and 8 weeks noise group（n=5）.Mean blood pressure（MBP） was measured through carotid cannulation.IVST,LPWT,EF and E/A were assessed by B-ultrasound.The left ventricular mass（LVM） and body mass（BM） were measured and LVMI（LVM/BM）was calculated.Immunohistochemistry and Western blot were used to evaluate the protein levels of GRP78 and CHOP.TUNNEL was used to detect the apoptosis in cardiac myocyte.Results ①The MBP in noise group was significantly higher than that in control group（P〈0.01）;②The IVST,LVPWT and LVMI increased by 29%,33%,38% in 4 week;29%,29%,33% in 6 weeks;23%,30%,26% in 8 weeks exposure group compared with control group（P〈0.05）.While E/A and EF value in noise group decreased at week 2 and week 6 respectively;③The expression of GRP78 in cardiac myocyte increased,reached its peak at week 4,and then declined.The protein level of CHOP was increased in a time-dependent manner.The expression of CHOP in noise groups was higher than the corresponding control group（P〈0.01）.Furthermore,the apoptosis in cardiac myocyte in noise groups also increased.Conclusion Noise stress could activate RES in myocyte.The abnormal expressions of GRP78 and CHOP could damage cardiac myocytes and increase apoptosis,which could be part of the potential mechanisms for hypertension,myocyte remodeling induced by noise stress.

关 键 词：噪声 心肌重构 内质网应激 葡萄糖调节蛋白78 CCAAT/增强子结合蛋白同源蛋白 凋亡 

分 类 号：R544.1[医药卫生—心血管疾病]