活血解毒降糖方对糖尿病大鼠动脉粥样硬化内质网应激的实验研究  

Experimentel Research of Huoxue Jiedu Jiangtang Formulation on Endoplasmic Reticulum Stress of Rats with Diabetic Atherosclerosis

作　　者：符显昭[1] 黄文华 王宁莉[1] 李星婵 丘海先[1] 曹秋夏 梁柳叶 FU Xianzhao;HUANG Wenhua;WANG Ningli;LI Xingchan;QIU Haixian;CAO Qiuxia;LIANG Liuye(Clinical Medical College,Youjiang Medical University for Nationalities,Baise 533099,Guangxi,China)

机构地区：[1]右江民族医学院临床医学院

出　　处：《中西医结合心脑血管病杂志》2019年第23期3702-3707,共6页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家自然科学基金地区项目(No.8146069,81960833);广西重点研发计划(No.2017AB45042);广西自然科学基金项目(No.2015GXNSFAA139221);广西自然科学基金(No.2019JJA,140146)

摘　　要：目的探讨活血解毒降糖方(HJJF)抑制糖尿病大鼠血管病变内质网应激偶联炎症反应的分子机制。方法采用高脂喂养+链脲佐菌素方法复制糖尿病模型,成模后随机分为模型组、HJJF低剂量组、HJJF高剂量组和西药组(格列喹酮+贝那普利),以相应的药物干预8周。另设正常组,予普通饲料喂养,不予药物干预。比较各组空腹血糖(FBG)、血脂、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的变化。检测主动脉内质网应激分子GRP78、JNK mRNA转录水平及细胞凋亡水平。结果与模型组相比,药物干预后,各给药组均能明显降低FBG(P<0.05),升高SOD、GSH-Px(P<0.05);均可降低总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、IL-6、TNF-α水平(P<0.05),升高高密度脂蛋白胆固醇(HDL-C)水平,比较差异有统计学意义(P<0.05);均可下调GRP78、JNK mRNA转录(P<0.05),降低细胞凋亡指数(P<0.05),以HJJF组疗效好,并随增加HJJF剂量更显著(P<0.05)。结论HJJF可抑制胰岛素抵抗,纠正脂质代谢紊乱,提高抗氧化应激能力,抑制内质网应激偶联炎症反应,体现了中医药多靶点的治疗特色。Objective To investigate the molecular mechanism of Huoxue Jiedu Jiangtang formulation(HJJF)in inhibiting endoplasmic reticulum stress(ERS)coupled inflammatory response in diabetic rats.Methods The diabetic model was established by feeding with high lipid diet and injection of streptozotocin.After models were established successfully,the rats were randomly divided into model group,HJJF low-dose group(HJJF1),HJJF high-dose group(HJJF2),and western medicine group(gliquidone and benazepril),with corresponding drug intervention for 8 weeks.The normal group was set up as control group,and the rats were fed with ordinary feed without drug intervention.The levels of fasting blood glucose(FBG),blood lipid,superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)were detected.The ERS signaling molecules glucose-regulated protein 78(GRP78)and c-Jun N-terminal kinases(JNK)mRNA level in thoracic aorta vessel were determined by reverse-transcription polymerase chain reaction(RT-PCR).Results Compared with the model group,FBG level was reduced,and SOD and GSH-Px level were elevated in administration group after intervention(P<0.05).The levels of total cholesterol,triacylglycerol,low-density lipoprotein cholesterol,IL-6,and TNF-αwere decreased(P<0.05),high-density lipoprotein cholesterol level was increased(P<0.05).GRP78 and JNK mRNA were down-regulated(P<0.05).The effect of HJJF group was better than that of other groups,which was more significant with the increase of HJJF dose(P<0.05).Conclusion HJJF can inhibit insulin resistance,improve lipid metabolism disorders,improve the ability of anti-oxidative stress,and inhibit ERS coupled with inflammatory response,which reflects the characteristics of multi-target treatment of traditional Chinese medicine.

关 键 词：糖尿病 动脉粥样硬化 活血解毒降糖方 炎症反应 内质网应激 实验研究 

分 类 号：R587[医药卫生—内分泌] R255.4[医药卫生—内科学]