摘要
目的:观察外源性给予硫化氢(H2S)供体硫氢化钠(Na HS)对大鼠糖尿病心肌病氧化应激作用以及内质网应激相关因子表达的影响。方法:将30只雄性SD大鼠随机分为对照组、糖尿病组和治疗组(n=10)。采用腹腔注射链脲佐菌素的方法制备大鼠糖尿病模型,治疗组采用腹腔注射给予Na HS干预治疗。12周后,利用离体心脏灌流装置测定心室动力学指标;透射电镜观察心肌细胞超微结构变化;测定心肌组织脂质过氧化物丙二醛(MDA)含量、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的活性;RT-PCR检测C/EBP同源蛋白(CHOP)、葡萄糖调节蛋白78(GRP78)和半胱天冬蛋白酶12(Caspase 12)基因表达。结果:与对照组比较,糖尿病组心功能明显降低、心肌超微结构损伤明显,心肌组织MDA含量增加、SOD和GSH-Px的活性明显降低,CHOP、GRP78和Caspase 12 mRNA表达明显增加。与糖尿病组比较,治疗组心功能和心肌超微结构损伤明显改善,心肌组织MDA含量下降,SOD和GSH-Px的活性明显升高,CHOP、GRP78和Caspase 12 mRNA表达明显下降。结论:外源性补充H2S对糖尿病大鼠心肌病具有保护作用,机制可能与减轻氧化应激损伤和抑制内质网应激引发的凋亡作用有关。
Objective： To investigate the effects of hydrogen sulfide （H2S） on oxidative stress and endoplasmic reticulum stress （ERS） in a rat model of diabetic cardiomyopathy （DCM）. Methods： Thirty male SD rats were randomly divided into control group, diabetes group and treatment group（ n = 10）. Intraperitoneal injection of streptozotocin was utilized to establish a rat model of DCM. The rats with DCM in treatment group were intraperitoneally injected with NariS solution. After treated for 12 weeks, the hearts isolated from rats were perfused on a langeudorff apparatus. The ventricular hemodynamic parameters were measured. The uhrastructures of myocardium were observed using electron microscopy. The content of malondialdehyde （MDA）, the activities of superoxide dismutase （SOl）） and glutathione peroxidase （GSH-Px） in myocardial tissue were determined by spectrophotometry. The expressions of C/EBP homologous protein（CHOP）, glucose-regulated protein 78 （GRP78） and Caspase 12 at mRNA level in myocardium were detected using RT-PCR. Results： Compared with control group, the cardiac function and myocardial ultrastructure were damaged obviously in diabetic rats. In myocardial tissue, the content of MDA was increased, while the activities of SOD and GSH-Px were decreased. CHOP, GRP78 and Caspase 12 mRNA expressions were increased significantly. Compared with diabetes group, cardiac function and myocardial ultrastructure damage were improved in treatment group. The content of MDA was decreased, while the activities of SOD and GSH-Px were increased significantly. The mRNA levels of CHOP, GRP78 and Caspase 12 were increased. Condusion： H2S can protect myocardium in diabetic rats, maybe it is related to reduce oxidative stress damage and inhibition of the ERS-induced apoptosis pathway.
出处
《中国应用生理学杂志》
CAS
CSCD
2016年第1期8-12,共5页
Chinese Journal of Applied Physiology
基金
国家自然科学基金(81000074)
安徽省教育厅自然科学研究项目(KJ2013B146
KJ2015B006by
KJ2015A163)
蚌埠医学院科研项目(BY0907
BYKY1312)
关键词
硫化氢
糖尿病心肌病
大鼠
氧化应激
内质网应激
hydrogen sulfide
diabetic cardiomyopathy
rat
oxidative stress
endoplasmic reticulum stress
