基于PI3K/Akt/GSK3β信号通路探讨苓桂气化方治疗射血分数保留心力衰竭的机制  

Discussion on the mechanism of Linggui Qihua Fomular in the treatment of heart failure with preserved ejection fraction based on PI3K/Akt/GSK3βsignaling pathway

作　　者：刘春秋 石玉姣 张贺[1] 杨晨光 乔文博 刘永成 刘思雨 董国菊[1] LIU Chunqiu;SHI Yujiao;ZHANG He;YANG Chenguang;QIAO Wenbo;LIU Yongcheng;LIU Siyu;DONG Guoju(First Department of Cardiology of Xiyuan Hospital of China Academy of Chinese Medical Sciences,Beijing 100091,China)

机构地区：[1]中国中医科学院西苑医院心血管一科,北京100091 [2]中国中医科学院研究生院

出　　处：《环球中医药》2024年第6期1014-1021,共8页Global Traditional Chinese Medicine

基　　金：国家自然科学基金(82074423);中国中医科学院科技创新重大攻关项目(CI2021A00903);中国中医科学院西苑医院提升中医药临床循证证据级别研究专项(XYZX0201-02)。

摘　　要：目的探讨苓桂气化方通过磷脂酰肌醇-3激酶(phosphoinositide-3 kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)/糖原合酶激酶3β(glycogen synthase kinase 3β,GSK3β)信号通路治疗射血分数保留心力衰竭(heart failure with preserved ejection fraction,HFpEF)的机制。方法将50只自发性高血压大鼠(spontaneous hypertensive rat,SHR)随机分为SHR组、HFpEF组、苓桂低组、苓桂高组和诺欣妥组,每组10只;另有10只WKY大鼠作为WKY组。采用喂食高盐高脂高糖饲料联合腹腔注射链脲佐菌素造模。造模后SHR组和WKY组给予生理盐水,其余组给予相应药物灌胃6周。分别于给药前后进行超声检测大鼠左心室前壁厚度(left ventricular anterior wall thickness,LVAWD)、左心室后壁厚度(left ventricular posterior wall thickness,LVPWD)、舒张末期左心室内径(left ventricular end diastolic internal diameter,LVEDD),以及左心房内径(left atrial diameter,LAD)和右心房内径(right atrial diameter,RAD)的左右径和前后径、左心室舒张早期充盈速度峰值(left ventricular early diastolic filling peak velocity,E)、心房收缩期左心室充盈速度峰值(atrial systolic left ventricular filling peak velocity,A)、舒张早期二尖瓣环血流速度峰值(early diastolic lateral mitral annulus velocity,e′)、E/A、E/e′、等容舒张时间(isovolumic relaxation time,IVRT)和左心室射血分数(left ventricular ejection fraction,LVEF);ELISA法检测心钠素(atrial natriuretic peptide,ANP)、脑钠肽(B-type natriuretic peptide,BNP);HE、Masson染色观察大鼠心肌组织结构和形态变化;Western blot法检测PI3K/Akt/GSK3β信号通路相关蛋白(Akt、PI3K、磷酸化PI3K、GSK3β、磷酸化GSK3β)的表达。结果苓桂气化方改善了HFpEF大鼠的心脏结构和功能,与HFpEF组相比:(1)超声结果显示:诺欣妥组、苓桂低组、苓桂高组大鼠的LVEDD、LVAWD、LVPWD、LAD、RAD、E/A、E/e′、IVRT值均显著降低(P<0.01),e′值显著升高(P<0.01),苓桂高组Objective To explore the mechanism of Linggui Qihua Formula(LGQHF)for the treatment of heart failure with preserved ejection fraction(HFpEF)based on phosphoinositide-3 kinase(PI3K)/protein kinase B(Akt)/glycogen synthase kinase-3beta(GSK3β)signaling pathway.Methods Fifty spontaneously hypertensive rats(SHR)and 10 Wistar-Kyoto(WKY)rats were randomly divided into the WKY group,the SHR group,the sakubutrazol valsartan sodium group,the HFpEF group,and the LGQHF low-dose group and the LGQHF high-dose group.with 10 rats in each group.The model was established by feeding high salt,high fat and high sugar diet combined with intraperitoneal injection of streptozotocin solution(STZ).Saline was given to the SHR and the WKY groups after modeling,and the remaining groups were gavaged with the corresponding drugs for 6 weeks.Ultrasound detection was performed before and after drug administration to detect the left ventricular anterior wall thickness(LVAWD),left ventricular posterior wall thickness(LVPWD),left ventricular end diastolic internal diameter(LVEDD),left atrial diameter(LAD)and right atrial diameter(RAD),left ventricular early diastolic filling peak velocity(E),atrial systolic left ventricular filling peak velocity(A),early diastolic lateral mitral annulus velocity(e′),E/A,E/e′,isovolumic relaxation time(IVRT)and left ventricular ejection fraction(LVEF).ELISA to detect atrial natriuretic peptide(ANP)and B-type natriuretic peptide(BNP).The structural and morphological changes of the myocardial tissues of the rat were observed by HE and Masson staining.Western blot to detect the expression of related proteins of PI3K/Akt/GSK3βsignaling pathway(Akt,PI3K,p-PI3K,GSK3β,p-GSK3β).Results Compared with the HFpEF group,LGQHF improved cardiac structure and function in HFpEF rats:(1)The results of Cardiac ultrasound showed that rats in the sakubutrazol valsartan sodium group,the LGQHF low-dose group and LGQHF high-dose group showed significant decreases in the values of LVEDD,LVAWD,LVPWD,LAD,RAD,E/A,E/e′,and IVRT(P<0.0

关 键 词：射血分数保留的心力衰竭 苓桂气化方 信号通路 心脏重构 舒张功能 

分 类 号：R285.5[医药卫生—中药学]