柚皮苷对糖尿病大鼠心肌病氧化应激及内质网应激的影响  

Effect of naringin on oxidative stress and endoplasmic reticulum stress in diabetic cardiomyopathy

作　　者：张羽飞 孟娜娜 李厚忠[3] 温以杰 刘洁婷 张春雷 袁晓环 金秀东[1,2] ZHANG Yu-fei;MENG Na-na;LI Hou-zhong;WEN Yi-jie;LIU Jie-ting;ZHANG Chun-lei;YUAN Xiao-huan;JIN Xiu-dong(Departraent of Physiology, School of Basic Medical Sciences, Heilongjiang University of Traditional Chin, ese Medicine Harbin 150040, China;Heilongjiang Key Laboratory of Anti-fibrosis Biotherapy, Mudanjiang Medical University, Mudanjiang 157011, China;Department of Pharmacy, Mudanjiang Medical Uaiversity, Mudanjiang 157011, China)

机构地区：[1]黑龙江中医药大学基础医学院生理教研室,黑龙江哈尔滨150040 [2]牡丹江医学院黑龙江省抗纤维化生物治疗重点实验室,黑龙江牡丹江157011 [3]牡丹江医学院药学院,黑龙江牡丹江157011

出　　处：《中国中药杂志》2018年第3期596-602,共7页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81573216);牡丹江医学院研究生创新科研项目(2016YJSCX-23MY,2017YJSCX-22MY)

摘　　要：探讨柚皮苷（naringin,Nar）对糖尿病大鼠心肌组织的保护作用与氧化应激及内质网应激的关系。SD雄性大鼠随机分为正常对照组（Con组）,模型组（T1DR组）,Nar低、中、高剂量组（Nar25,Nar50,Nar100）。除Con组外,其他各组用链脲佐菌素（STZ,60 mg·kg^-1）一次性腹腔注射建立糖尿病大鼠模型,模型复制成功后Nar分别按25.0,50.0,100.0 mg·kg^-1剂量灌胃;Con组和T1DR组等体积生理盐水灌胃,每天1次,连续8周。8周后处死大鼠,留取心肌组织。普通光镜观察大鼠心肌组织病理改变。试剂盒法检测心肌组织超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量。实时荧光定量PCR（qRT-PCR）和Western blot法检测各组大鼠心肌组织葡萄糖调节蛋白78（GRP78）,CCAAT/增强子结合蛋白同源蛋白（CHOP）、天冬氨酸特异性半胱氨酸蛋白酶12（caspase 12）mRNA和蛋白的表达。结果显示,与Con组比较,T1DR组心肌结构发生损伤,心肌组织MDA含量增加（P〈0.05）、SOD的活性明显降低（P〈0.05）。内质网应激相关因子GRP78,CHOP和caspase 12基因和蛋白表达明显增加（P〈0.05或P〈0.01）。Nar处理8周后,Nar各干预组心肌结构损伤明显改善,心肌组织MDA含量下降,SOD的活性明显升高,GRP78,CHOP和caspase 12基因和蛋白表达明显下降,其中中、高剂量组变化显著（P〈0.05,P〈0.01）。该研究结果表明,Nar可能通过减轻大鼠糖尿病心肌氧化应激损伤,抑制内质网应激启动的细胞凋亡途径发挥对心肌组织细胞的保护作用。To explore the protective effect of naringin（ Nar） on the injury of myocardium tissues induced by streptozotocin（ STZ）in diabetic rats and the relationship with oxidative stress and endoplasmic reticulum stress（ ERS）,the male SD rats were intraperitoneally injected with streptozotocin（ STZ,60 mg·kg^-1） to establish the diabetic rat model and then randomly divided into the type 1 diabetic rat group（ T1 DR）,the low-dose Nar group（ Nar25）,the middle-dose Nar group（ Nar50） and the high-dose Nar group（ Nar100）. The normal rats were designed as control group（ Con）. Nar25,Nar50,Nar100 groups were orally administered with Nar at the doses of 25. 0,50. 0,100. 0 mg·kg^-1 per day,respectively,while the normal group and the T1 DR group were orally administered with saline. At the 8 thweek after treatment,fasting plasma glucose and heart mass index were measured. The pathological changes in myocardial tissues were observed by microscope. The cardiac malondialdehyde（ MDA） level and superoxide dismutase（ SOD） activities were measured. The gene and protein expressions of glucose-regulated protein 78（ GRP78）, C/EBP homologous protein（ CHOP）,cysteinyl aspartate-specific proteinase 12（ caspase 12） were detected by qRT-PCR and Western blot. According to the results,compared with control group,the myocardial structure was damaged,the content of MDA was increased,while the activities of SOD were decreased（ P〈0. 05） in T1 DR group. GRP78,CHOP and caspase 12 mRNA and protein expressions were increased significantly in T1 DR group（ P〈0. 05,P〈0. 01）. Compared with T1 DR group,myocardial structure damage was alleviated in Nar treatment group. The content of MDA was decreased,while the activities of SOD were increased significantly. The mRNA and protein expressions of GRP78,CHOP and caspase 12 were increased,especially in middle and high-dose groups（ P〈0. 05,P〈0. 01）. After treatment with Nar for 8 weeks,myocardial structure damage was obviously alleviated in Na

关 键 词：柚皮苷 糖尿病心肌病 内质网应激 氧化应激 

分 类 号：R285.5[医药卫生—中药学]