复方丹参滴丸通过调控IRE1-TRAF2-ASK1-JNK通路降低内质网应激和自噬保护血管平滑肌细胞  

Fufang Danshen dripping pills protect vascular smooth muscle cells by reducing endoplasmic reticulum stress and autophagy through regulating IRE1-TRAF2-ASK1-JNK pathway

作　　者：李幸幸 刘俊[1] 徐忠诚 邹晋 董扬[1] LI Xing-xing;LIU Jun;XU Zhong-cheng;ZOU Jin;DONG Yang(Dept of Cardiology,Jinhua People s Hospital,Jinhua,Zhejiang 321000,China;Jiangxi Institute of Cardiovascular Diseases,Jiangxi Provincial People s Hospital,Nanchang 330006,China)

机构地区：[1]浙江省金华市人民医院心血管内科,浙江金华321000 [2]江西省人民医院江西省心血管病研究所,江西南昌330006

出　　处：《中国药理学通报》2022年第5期776-783,共8页Chinese Pharmacological Bulletin

基　　金：浙江省自然科学基金探索项目(No LQ21H020002);金华市科学技术研究计划社发类重点项目(No 2020-3-060)。

摘　　要：目的探讨复方丹参滴丸通过调控内质网应激和自噬保护血管平滑肌细胞的分子机制。方法50例动脉粥样硬化患者随机分为两组,一组正常治疗,另一组加入复方丹参滴丸并进行临床疗效观察。将血管平滑肌细胞分为对照组、ox-LDL模型组、复方丹参滴丸组、复方丹参滴丸+内质网应激抑制剂组、复方丹参滴丸+内质网应激诱导剂组。检测增殖情况,测定各组血管细胞舒张功能因子与氧化应激情况,分别检测内质网应激标志蛋白,自噬标志蛋白及凋亡相关蛋白表达情况,并检测IRE1-TRAF2-ASK1-JNK信号通路的激活情况。结果与对照组相比,ox-LDL模型组细胞的各项指标显示其处于内质网应激、高氧化应激、高自噬状态,并且发现IRE1-TRAF2-ASK1-JNK通路被过度激活。而与ox-LDL模型组相比,复方丹参滴丸组和复方丹参滴丸+内质网应激抑制剂组的上述指标均明显好转,IRE1-TRAF2-ASK1-JNK通路被过度激活得到改善,且内质网应激抑制剂更为明显,复方丹参滴丸+内质网应激诱导剂组则明显逆转了复方丹参滴丸的好转。结论复方丹参滴丸通过抑制IRE1-TRAF2-ASK1-JNK通路的过度激活,降低内质网应激,维持适当自噬,抑制细胞异常增殖和凋亡,从而保护血管平滑肌细胞。Aim To investigate the molecular mechanism of the protection of vascular smooth muscle cells by the regulation of endoplasmic reticulum stress and autophagy by Fufang Danshen dripping pills.Methods Fifty patients with atherosclerosis were randomly divided into two groups;one group received normal treatment,while the other group was added Fufang Danshen dripping pills,and the clinical efficacy was observed.Vascular smooth muscle cells were divided into control,ox LDL model,Fufang Danshen dripping pill group,Fufang Danshen dripping pill+endoplasmic reticulum stress inhibitor group,and Fufang Danshen dripping pill+endoplasmic reticulum stress inducer group.Proliferation was detected,and vasodilator function factors and oxidative stress were measured in each group,ER stress marker proteins,autophagy marker proteins and apoptosis related protein expression were detected,and activation of the IRE1-TRAF2-ASK1-JNK signaling pathway was detected.Results Compared with control group,various indicators of cells in ox-LDL model group showed that they were under ER stress,high oxidative stress,high autophagy status,and the IRE1-TRAF2-ASK1-JNK pathway was found to be over activated.However,compared with ox LDL model group,the above indicators in Fufang Danshen dripping pill group and Fufang Danshen dripping pill+endoplasmic reticulum stress inhibitor group were significantly better,the IRE1-TRAF2-ASK1-JNK pathway was over activated,and the endoplasmic reticulum stress inhibitor was more obvious,and Fufang Danshen dripping pill+endoplasmic reticulum stress inducer group significantly reversed the improved effects of Fufang Danshen dripping pills.Conclusions Fufang Danshen dripping pills protect vascular smooth muscle cells by inhibiting excessive activation of the IRE1-TRAF2-ASK1-JNK pathway,decreasing endoplasmic reticulum stress,maintaining proper autophagy,and inhibiting abnormal cell proliferation and apoptosis.

关 键 词：复方丹参滴丸 血管平滑肌细胞 IRE1-TRAF2-ASK1-JNK通路 内质网应激 自噬 

分 类 号：R282.71[医药卫生—中药学] R322.74[医药卫生—中医学]