豁痰解毒通络饮通过内质网应激-线粒体凋亡途径干预大鼠颈总动脉球囊损伤后再狭窄的作用机制  

The Mechanism of Huotan Jiedu Tongluo Yin on Restenosis after Balloon Injury of Common Carotid Artery in Rats through Endoplasmic Reticulum Stress-mitochondrial Apoptosis Pathway

作　　者：田腾辉 邓悦[2] Tumurkhuyag Atartsetseg 常立萍[2] 石锐[2] 于克英 张淼 TIAN Tenghui;DENG Yue;Tumurkhuyag Atartsetseg;CHANG Liping;SHI Rui;YU Keying;ZHANG Miao(Changchun University of Chinese Medicine,Changchun 130117,Jilin,China,The Affiliated Hospital of Changchun University of Chinese Medicine,Changchun 130021,Jilin,China)

机构地区：[1]长春中医药大学,长春130117 [2]长春中医药大学附属医院,长春130021

出　　处：《中西医结合心脑血管病杂志》2022年第8期1387-1391,共5页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家自然科学基金面上项目(No.81774226);国家重点研发计划项目(No.2019YFC1709901);吉林省科技发展计划自然科学基金项目(No.20180101149JC)。

摘　　要：目的探讨豁痰解毒通络饮对经皮冠状动脉介入(PCI)术后再狭窄的治疗作用及可能机制。方法将雄性SD大鼠24只按照随机数字法分为假手术组(Sham组)、球囊损伤模型组(模型组)、豁痰解毒通络饮组(中药组)及阿托伐他汀组(西药组),每组6只。采用2F Fogarty球囊建立大鼠颈总动脉球囊损伤模型,于术后4周取损伤段颈动脉,苏木精-伊红(HE)染色观察颈动脉血管形态学改变并评估内膜增生情况。免疫组化法检测血管组织C/EBP同源蛋白(CHOP)表达;蛋白免疫印迹法检测大鼠颈总动脉中蛋白激酶R样内质网激酶(PERK)、CHOP、Bax、Bcl-2蛋白表达;实时荧光定量聚合酶链式反应(RT-qPCR)检测颈动脉CHOP、Bax mRNA表达。结果与Sham组比较,模型组大鼠颈总动脉内膜增生,管腔内径变窄,损伤段血管CHOP阳性表达率明显升高,PERK、CHOP、Bax蛋白表达水平及CHOP、Bax mRNA表达较Sham组升高(P<0.05),Bcl-2蛋白表达降低(P<0.01),Bcl-2/Bax比值降低(P<0.01)。与模型组比较,中药组和西药组内膜增生及管腔狭窄情况均明显减轻;损伤段血管CHOP阳性表达率明显降低;PERK、CHOP、Bax蛋白表达及CHOP、Bax mRNA表达降低(P<0.05),Bcl-2蛋白表达升高(P<0.05),且Bcl-2/Bax比值升高(P<0.05)。结论豁痰解毒通络饮可能通过降低球囊损伤术后颈动脉中内质网应激反应,从而减轻线粒体凋亡激活,发挥抑制内膜增生,预防再狭窄的作用。Objective To explore the therapeutic effect of Huodan Jiedu Tongluo Yin on restenosis after percutaneous coronary intervention(PCI)and its possible mechanism.Methods Twenty-four male SD rats were randomly divided into Sham group(Sham group),balloon injury model group(model group),Huotan Jiedu Tongluo Yin group(traditional Chinese medicine group)and atorvastatin group(western medicine group),with 6 rats in each group.The balloon injury model of the rat common carotid artery was established by 2F Fogarty balloon.The injured carotid artery was taken 4 weeks after surgery.The morphological changes of the carotid artery were detected by hematoxylin-eosin(HE)to evaluate the intimal hyperplasia.The expression of C/EBP homoiogous protein(CHOP)in vascular tissues was detected by immunohistochemistry.The protein expression of proteinkinase R-like ER kinase(PERK),CHOP,and Bax and Bcl-2 in the carotid arteries was detected by Western Blotting.The mRNA expressions of CHOP and Bax in the carotid artery were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Results Compared with Sham group,the intima hyperplasia of the common carotid artery was significantly proliferated and lumen diameter was narrowed in the model group,the positive expression rate of CHOP in injured vessels was increased significantly,the protein expressions of PERK,CHOP,Bax and the mRNA expressions of CHOP and Bax were increased(P<0.05),while the protein expression of Bcl-2 was decreased(P<0.01),and Bcl-2/Bax ratio was decreased(P<0.01).Compared with model group,intimal hyperplasia and lumen stenosis were significantly relieved in the traditional Chinese medicine group and western medicine group,the positive expression rate of CHOP in injured vessels was decreased significantly,the protein expressions of PERK,CHOP,Bax and the mRNA expressions of CHOP and Bax were decreased(P<0.05),while the protein expression of Bcl-2 was increased(P<0.05),and Bcl-2/Bax ratio was increased(P<0.05).Conclusion Huotan Jiedu Tongluo Yin might red

关 键 词：心血管疾病 经皮冠状动脉介入 豁痰解毒通络饮 球囊损伤 再狭窄 内质网应激 凋亡 大鼠 实验研究 

分 类 号：R73[医药卫生—肿瘤]