化痰祛瘀法调控miR-17-5p防治动脉粥样硬化的作用机制研究  

Mechanism of Huatan Quyu Therapy in Preventing and Treating Atherosclerosis by Regulating miR-17-5p

作　　者：王付启 李文涛 王媛[2] 秦合伟[2] WANG Fuqi;LI Wentao;WANG Yuan;QIN Hewei(Zhumadian Hospital of Traditional Chinese Medicine,Zhumadian 463000,China;The Second Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China)

机构地区：[1]驻马店市中医院,河南驻马店463000 [2]河南中医药大学第二附属医院,河南郑州450000

出　　处：《中医药信息》2021年第9期22-26,共5页Information on Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81704030);河南省中医药科学研究专项重点课题(2019ZY1015);河南省科技攻关计划项目(212102310359);河南省中医药拔尖人才培养项目(豫卫中医函〔2021〕15号)。

摘　　要：目的:观察化痰祛瘀法防治动脉粥样硬化的作用机制是否与靶向调控miR-17-5p影响PCSK9/VLDLR信号通路有关。方法:15只C57BL/6小鼠作为对照组,60只ApoE-/-小鼠随机分为模型组、miR-17-5p inhibitor组、化痰祛瘀法高剂量组(高剂量组)和化痰祛瘀法低剂量组(低剂量组),每组各15只;连续干预8周后检测各组小鼠外周血清中IL-6、IL-10、TNF-α水平,主动脉中miR-17-5p、VLDLR、PCSK9 mRNA和蛋白表达水平,并进行病理学观察。结果:与模型组相比,miR-17-5p inhibitor组、高剂量组、低剂量组外周血清中IL-6、IL-10和TNF-α水平明显降低(P<0.05),与模型组相比,miR-17-5p inhibitor组、高剂量组、低剂量组主动脉miR-17-5p和VLDLRmRNA和蛋白表达均明显降低(P<0.05),PCSK9 mRNA和蛋白表达水平均明显升高(P<0.05);病理检测结果显示,miR-17-5p inhibitor组、高剂量组、低剂量组的动脉粥样硬化程度明显较轻。结论:化痰祛瘀法抗动脉粥样硬化的作用机制可能与靶向调控miR-17-5p影响PCSK9/VLDLR信号通路,抑制血管炎性反应,减轻内皮细胞损伤有关。Objective:To observe whether the anti-atherosclerosis mechanism of Huatan Quyu(resolving phlegm and removing blood stasis)therapy is related to the targeted regulation of miR-17-5p affecting the PCSK9/VLDLR signaling pathway.Methods:15 C57BL/6 mice were used as the control,and 60 ApoE-/-mice were divided into the model group,the miR-17-5p inhibitor group,the Huatan Quyu groups of high-dose and low-dose,with 15 mice in each group.After 8 weeks of continuous intervention,the serum levels of IL-6,IL-10 and TNF-αwere measured,and the mRNA and protein expressions of miR-17-5p,VLDLR and PCSK9 in the aorta were detected,and pathological changes were observed in each group.Results:The serum levels of IL-6 and TNF-αsignificantly decreased(P<0.05),and the serum level of IL-10 significantly increased in the miR-17-5p inhibitor group and the Huatan Quyu groups of high-dose and low-dose compared to those in the model group(P<0.05).The mRNA and protein expressions of miR-17-5p and VLDLR were down-regulated(P<0.05),and the mRNA and protein expressions of PCSK9 were up-regulated in the miR-17-5p inhibitor group and the Huatan Quyu groups of high-dose and low-dose compared to those in the model group(P<0.05).The pathological test results showed that the atherosclerosis was less severe in the miR-17-5p inhibitor group and the Huatan Quyu groups of high-dose and low-dose.Conclusion:The anti-atherosclerosis mechanism of Huatan Quyu therapy may be related to the targeted regulation of miR-17-5p,which affects the PCSK9/VLDLR signaling pathway,inhibits vasculitis and reduces endothelial cells damage.

关 键 词：动脉粥样硬化 化痰祛瘀法 微小核糖核酸17-5p 极低密度脂蛋白受体 前蛋白转化酶枯草溶菌素9 

分 类 号：R285.5[医药卫生—中药学]