糖尿病大鼠心肌组织内质网应激因子GRP78及caspase-12的表达及其对心脏结构和功能的影响  

Expression of endoplasmic reticulum stress-related GRP78 and caspase-12 in myocardial tissue of diabetic rats and its effect on cardiac structure and function

作　　者：杨竞霄[1] 陈静园 王子宽[1] 

机构地区：[1]第四军医大学附属唐都医院心内科,西安710038 [2]火箭军工程大学门诊部

出　　处：《山西医科大学学报》2016年第8期679-684,共6页Journal of Shanxi Medical University

摘　　要：目的观察糖尿病大鼠心肌内质网应激(endoplasmic reticulum stress,ERS)相关因子GRP78和caspase-12表达的变化,探讨其对心脏结构和功能的影响。方法采用链脲佐菌素腹腔注射制备糖尿病大鼠模型,取15只造模成功的大鼠,随机分为0周组、8周组和16周组,每组5只。采用颈动脉插管法检测大鼠血压、心率及心功能的各项指标。称取体质量、全心质量及左心室质量,计算大鼠心肌肥厚指数HWI及LVEI。Masson染色观察心肌胶原纤维含量的改变,免疫组化及Western blot检测大鼠心肌组织中GRP78及caspase-12表达水平,Western blot检测cleaved caspase-3表达水平。结果三组大鼠血压及心率无统计学差异(P>0.05)。与0周组相比,大鼠平均左心室舒张末期压(LVEDP)及平均压下降最大速率(-dp/dtmax)在8周及16周时明显升高(P<0.05);平均压力上升最大速率(+dp/dtmax)在16周时明显降低(P<0.05)。与0周组相比,大鼠心肌肥厚指标HWI及LVWI在8周时无明显变化(P>0.05),HWI及LVWI在16周时明显升高(P<0.05)。与0周组相比,大鼠心肌Masson染色在8周和16周时心肌细胞排列紊乱,胶原纤维明显增多。与0周组相比,免疫组化及Western blot检测大鼠心肌组织GRP78表达8周时明显增高(P<0.05),16周时GRP78表达明显降低(P<0.05);caspase-12表达在8周时明显增高(P<0.05),16周时显著增高(P<0.01);Western blot检测cleaved caspase-3表达在8周时明显增高(P<0.05),在16周时显著增高(P<0.01)。结论高血糖可以直接影响大鼠心肌结构和功能。高血糖早期GRP78表达的升高;随应激时间的延长,caspase-12及cleaved caspase-3表达明显升高。因此,心肌细胞ERS的激活可能是高血糖所致大鼠心肌结构和功能改变的原因之一。Objective To investigate the expression of endoplasmic reticulum stress（ ERS） -related GRP78 and caspase-12 in myocardial tissues of diabetic rats, and explore the effect of ERS on cardiac structure and function. Methods Fifteen diabetic rat models were induced by streptozotocin（STZ） and then randomly divided into 0 week group, 8 weeks group, and 16 weeks group. Blood pressure, heart rate and myocardial function were measured by carotid artery intubation indicator. Heart weight to body weight ratio （ HWI）, left ventricular weight to whole heart weight（LVWI） were calculated, and collagenous fiber was observed by Masson staining. The expression levels of GRP78, caspase-12 and cleaved caspase-3 in rat myocardial tissues were measured. Results Compared with 0 week group, left ventricular end-diastolic pressure （LVEDP） and -dp/dtmax were increased in 8 weeks group （P 〈 0. 05 ） and 16 weeks group（P 〈 0. 01 ）. Compared with 0 week group, HWI and LVWI were increased in 16 weeks group（P 〈 0.05 ）. Collagenous fiber was slight, whereas it was increased in 8 weeks group. Compared with 0 week group, the expression of GRP78 significantly up-regulated in 8 weeks group（P 〈 0.01 ）, but down-regulated in 16 weeks group （P 〈 0. 05 ）. The expression of caspase-12 and cleaved caspase-3 were markedly increased in 8 weeks and 16 weeks group （P 〈 0. 05 ）. Conclusion Hyperglycemia could exert a direct effect on heart in rats. In the early stage of hyperglycemia, the expression of GRP78 protein is up-regulated, and the expression of caspase-12 and cleaved caspase-3 is also significantly up-regulated as the stress is enlarged. The ERS of myocardial tissues could be one of the reasons of the changes of cardiac structure and function in diabetic rats.

关 键 词：糖尿病 内质网应激 心脏结构 GRP78 CASPASE-12 大鼠 

分 类 号：R587.1[医药卫生—内分泌]