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