基于“痰瘀生风”理论研究中药复方调控TGF-β1/Smad2/3/α-SMA信号通路治疗痰浊血瘀型PAF的机制研究  

Based on the theory of"phlegm and blood stasis generating wind",the mechanism of tra-ditional Chinese medicine compound regulating TGF-β1/Smad2/3/α-SMA signaling pathway to improve PAF

作　　者：颜晓睿 吴启华 赵帅 宫丽鸿[1,3] YAN Xiao-rui;WU Qi-hua;ZHAO Shuai;GONG Li-hong(Liaoning University of Traditional Chinese Medicine,Shenyang 110032,China;Center of Traditional Chinese Medicine Innovation Engineering Technology,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110032 [2]辽宁中医药大学中医药创新工程技术中心,辽宁沈阳110847 [3]辽宁中医药大学附属医院,辽宁沈阳110032

出　　处：《时珍国医国药》2023年第6期1334-1337,共4页Lishizhen Medicine and Materia Medica Research

基　　金：辽宁省应用基础研究计划项目(2022JH21101300086);辽宁省重点实验室建设项目(2022JH13110200027)。

摘　　要：目的基于“痰瘀生风”理论,以转化生长因子-β1(TGF-β1)/Smad2/3/α-平滑肌肌动蛋白(α-SMA)信号通路为切入点探究中药复方抑制心房纤维化,改善痰浊血瘀型阵发性房颤大鼠心房重构的可能机制。方法将60只SD大鼠,随机分为对照组、模型组、中药复方高剂量组、中药复方中剂量组、中药复方低剂量组和维拉帕米组(n=10)。采用尾静脉注射乙酰胆碱-氯化钙(Ach-CaCl2)联合喂养高脂饲料方法建立痰浊血瘀型阵发性房颤大鼠模型,造模成功后,第2天开始灌胃,对照组及模型组采用等体积生理盐水灌胃,中药复方高剂量41.25g/(kg·d)、中剂量20.63g/(kg·d)、低剂量10.31g/(kg·d),日1次灌胃,维拉帕米组维拉帕米溶液25mg/(kg·d)日1次灌胃,用药干预2周后,心电图记录各组大鼠房颤持续时间、透射电镜观察大鼠心房肌组织超微结构,运用Western Blot法检测心房TGF-β1、Smad2/3、α-SMA蛋白表达。结果心电图显示造模成功,且与模型组相比,中药复方各剂量组及维拉帕米组大鼠房颤持续时间显著缩短(P<0.05);透射电镜下观察到心房肌细胞的肌小节轻微断裂,肌丝间未出现间隙;同时TGF-β1、Smad2/3、α-SMA表达显著下降(P<0.05)。结论中药复方可能通过调控TGF-β1/Smad/α-SMA通路相关蛋白的表达,抑制心房纤维化,改善心房重构,进而减少阵发性房颤的发生。Objective Based on the theory of"phlegm and blood stasis generating wind",taking TGF-β1/Smad2/3/α-SMA signaling pathway as an entry point to explore traditional Chinese medicine compounds to inhibit atrial fibrosis and improve parox-ysmal atrial phlegm and blood stasis type Possible mechanisms of atrial remodeling in fibrillating rats.Methods 60 SD rats were randomly divided into control group,model group,high-dose Chinese herbal compound group,Chinese herbal compound medi-um-dose group,Chinese herbal compound low-dose group and verapamil group(n=10).A rat model of paroxysmal atrial fi-brillation with phlegm turbidity and blood stasis was established by tail vein injection of acetylcholine-calcium chloride(Ach-CaCl2)combined with high-fat diet.The model group was given an equal volume of normal saline by gavage,and the high dose of traditional Chinese medicine compound was 41.25g/(kg·d),the middle dose was 20.63g/(kg·d),and the low dose was 10.31g/(kg·d),once a day,verapamil group verapamil solution 25mg/(kg·d)once a day by intragastric administration,af-ter 2 weeks of drug intervention,the duration of atrial fibrillation in each group was recorded by electrocardiogram,and the atrial myocardium was observed by transmission electron microscope.Microstructure,the expression of TGF-β1,Smad2/3,α-SMA protein in atrial was detected by Western Blot method.Results The electrocardiogram showed that the modeling was successful,and compared with the model group,the duration of atrial fibrillation was significantly shortened in each dose group and verapamil group(P<0.05).There was no gap between the myofilaments;meanwhile,the expressions of TGF-β1,Smad2/3 andα-SMA decreased significantly(P<0.05).Conclusion The traditional Chinese medicine compound may inhibit atrial fibrosis and im-prove atrial remodeling by regulating the expression of TGF-β1/Smad/α-SMA pathway-related proteins,thereby reducing the occurrence of paroxysmal atrial fibrillation.

关 键 词：中药复方 痰瘀生风 阵发性房颤 心房重构 转化生长因子-β1/Smad2/3/α-平滑肌肌动蛋白信号通路 

分 类 号：R285.5[医药卫生—中药学]