甘草素调节LKB1/AMPK信号通路对冠心病大鼠的心脏保护作用研究

Study on Protective Effect of Liquiritigenin on the Heart of Rats with Coronary Heart Disease by Regulating LKB1/AMPK Signal Pathway.

目的探讨甘草素(Liq)调节肝激酶B1(LKB1)/腺苷酸激活蛋白激酶(AMPK)信号通路对冠心病大鼠的心脏保护作用。方法Wistar大鼠随机分为对照组及造模组,造模组通过高脂饲料喂养以及腹腔注射垂体后叶素建立冠心病大鼠模型,将造模成功的冠心病大鼠随机分为冠心病组、Liq低剂量(Liq-L)组(100 mg/kg Liq)、Liq高剂量(Liq-H)组(300 mg/kg Liq)、Liq-H+Radicicol组(300 mg/kg Liq+40 mg/kg Radicicol)。干预结束后,检测心功能[左心室收缩末期直径(LVSD)、射血分数(EF)、左心室舒张末期直径(LVDD)和左心室缩短分数(FS)]及血脂水平[总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)和低密度脂蛋白(LDL)];ELISA检测血清中炎性因子[白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α]及氧化应激因子[谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和丙二醛(MDA)]水平;分离心脏组织,HE染色观察组织病理变化;Western Blot检测p-AMPK/AMPK、LKB1表达水平。结果与对照组相比,冠心病组大鼠心脏组织排列紊乱,有大量炎性细胞浸润,大鼠IL-1β、IL-6、TNF-α水平、TC、TG、LDL、LVSD、LVDD、MDA显著增加,p-AMPK/AMPK、LKB1表达、HDL、EF、FS、SOD、GSH显著降低(P<0.05);与冠心病组相比,Liq-L组、Liq-H组病理损伤得到缓解,IL-1β、IL-6、TNF-α水平、TC、TG、LDL、LVSD、LVDD、MDA显著降低,p-AMPK/AMPK、LKB1表达、HDL、EF、FS、SOD、GSH显著增加(P<0.05);与Liq-H组相比,Liq-H+Radicicol组病理损伤加重,IL-1β、IL-6、TNF-α水平、TC、TG、LDL、LVSD、LVDD、MDA显著增加,p-AMPK/AMPK、LKB1表达、HDL、EF、FS、SOD、GSH显著降低(P<0.05)。结论Liq可能通过激活LKB1/AMPK信号通路发挥对冠心病大鼠心脏的保护作用。

Objective To investigate protective effects of liquiritigenin(Liq)on the heart of rats with coronary heart disease by regulating liver kinase B1(LKB1)/adenylate activated protein kinase(AMPK)signal pathway.Methods Wistar rats were randomly divided into control group and model group.The model group was fed with high-fat diet and intraperitoneal injection of pituitrin to establish the rat model of coronary heart disease,the coronary heart disease rats with successful modeling were randomly divided into coronary heart disease group,Liq low dose(Liq-L)group(100 mg/kg Liq),Liq high dose(Liq-H)group(300 mg/kg Liq),and Liq-H+Radicicol group(300 mg/kg Liq+40 mg/kg Radicicol).After intervention,serum was collected to detect cardiac function[left ventricular end systolic diameter(LVSD),ejection fraction(EF),left ventricular end diastolic diameter(LVDD),left ventricular shortening fraction(FS)]and blood lipid levels[total cholesterol(TC),triglyceride(TG),high-density lipoprotein(HDL)and low-density lipoprotein(LDL)].Serum inflammatory factor[interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α)]and oxidative stress factor[glutathione(GSH),superoxide dismutase(SOD)and malondialdehyde(MDA)]were detected by ELISA.Cardiac tissue was isolated,HE staining was used to observe histopathological changes.And Western blot was used to detec p-AMPK/AMPK and LKB1 in tissues.Results Compared with control group,cardiac tissue of rats in the coronary heart disease group was in disorder,with a large number of inflammatory cells infiltrating,IL-1β,IL-6,TNF-α,TC,TG,LDL,LVSD,LVDD and MDA in rats increased obviously.However,p-AMPK/AMPK,LKB1,HDL,EF,FS,SOD and GSH decreased obviously(P<0.05).Compared with coronary heart disease group,pathological damage in Liq-L group and Liq-H group was alleviated,IL-1β,IL-6,TNF-α,TC,TG,LDL,LVSD,LVDD and MDA decreased obviously,however,p-AMPK/AMPK and LKB1,HDL,EF,FS,SOD and GSH increased obviously(P<0.05).Compared with Liq-H group,pathological damage in Liq-H+Radicol group was aggravated,IL-1β,IL-6,TNF-α,TC,TG,LDL,LVSD,LVDD and MDA in rats increased obviously.However,p-AMPK/AMPK,LKB1,HDL,EF,FS,SOD and GSH decreased obviously(P<0.05).Conclusion Liq could protect heart of coronary heart disease rats by activating LKB1/AMPK signal pathway.