花黄色素调节AMPK/SIRT1/NF-κB信号通路对冠心病大鼠心肌损伤的影响  

Influence of Safflower Yellow on Myocardial Injury of Rats with Coronary Heart Disease by Regulating AMPK/SIRT1/NF-κB Signaling Pathway

作　　者：包立民 姜焜 王菊 黄方 陈霞 BAO Limin;JIANG Kun;WANG Ju;HUANG Fang;CHEN Xia(Second Hospital of Huangshi City,Huangshi 435002,Hubei,China)

机构地区：[1]黄石市第二医院,湖北黄石435002 [2]湖北文理学院附属医院,襄阳市中心医院,湖北襄阳441021

出　　处：《中西医结合心脑血管病杂志》2024年第16期2932-2937,共6页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：湖北省自然科学基金(No.WJ2018Z0118)。

摘　　要：目的:探讨花黄色素(SY)调控腺苷酸活化蛋白激酶(AMPK)/沉默信息调节因子1(SIRT1)/核转录因子-κB(NF-κB)对冠心病(CHD)大鼠心肌损伤的影响。方法:将60只SD大鼠随机分为正常对照组(NC组,生理盐水)、模型组(Model组,生理盐水)、SY组(100 mg/kg SY)、EX-527组(47 mg/kg EX-527)、SY+EX-527组(100 mg/kg SY+47 mg/kg EX-527),每组12只,持续4周给予相应药物。试剂盒检测血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)水平和心肌白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平;苏木素-伊红(HE)染色法进行心肌组织病理学观察;末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)法检测心肌细胞凋亡情况;蛋白免疫印迹(Western Blot)法检测心肌组织AMPK/SIRT1/NF-κB通路相关蛋白表达。结果:与NC组相比,Model组大鼠心肌细胞数量少且排列杂乱,细胞核皱缩,TC、TG、LDL-C、氧化修饰低密度脂蛋白(ox-LDL)、IL-6、TNF-α水平、心肌细胞凋亡率及NF-κB蛋白水平明显上升(P<0.05),SOD、GSH-Px水平及磷酸化-AMPK(p-AMPK)/AMPK、SIRT1蛋白水平明显下降(P<0.05)。与Model组比较,SY组大鼠心肌细胞数量增多且排列整齐有序,TC、TG、LDL-C、ox-LDL、IL-6、TNF-α水平、心肌细胞凋亡率及NF-κB蛋白水平明显下降(P<0.05),SOD、GSH-Px水平及p-AMPK/AMPK、SIRT1蛋白水平明显上升(P<0.05);而EX-527组以上指标呈现相反趋势。与SY组相比,SY+EX-527组大鼠心肌损伤加重,TC、TG、LDL-C、ox-LDL、IL-6、TNF-α水平、心肌细胞凋亡率及NF-κB蛋白水平明显上升(P<0.05),SOD、GSH-Px水平及p-AMPK/AMPK、SIRT1蛋白水平明显下降(P<0.05)。结论:SY可能通过调控AMPK/SIRT1/NF-κB通路降低氧化应激,减轻炎症反应,对冠心病大鼠心肌损伤起到一定改善作用。Objective:To investigate the influence of safflower yellow(SY)on myocardial injury of rats with coronary heart disease(CHD)by regulating AMP-activated protein kinase(AMPK)/silent information regulator 1(SIRT1)/nuclear transcription factor-κB(NF-κB).Methods:Sixty SD rats were randomly grouped into NC group(normal saline),Model group(normal saline),SY group(100 mg/kg SY),EX-527 group(47 mg/kg EX-527),and SY+EX-527 group(100 mg/kg SY+47 mg/kg EX-527),with 12 rats in each group,the corresponding drugs were given for 4 weeks.The kits were used to detect serum triacylglycerol(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)levels and myocardial interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)levels.Hematoxylin eosin(HE)staining was used for the histopathological observation of myocardial cells.Terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL)method was applied to detect cardiomyocyte apoptosis.Western Blot was used to detect the expression of AMPK/SIRT1/NF-κB pathway-related proteins in myocardial tissue.Results:Compared with NC group,the number of cardiomyocytes in Model group was less and the arrangement was disorderly,and the nuclei were shrunken,the levels of TC,TG,LDL-C,oxidized low density lipoprotein(ox-LDL),IL-6,TNF-α,the apoptosis rate of cardiomyocytes,and the protein level of NF-κB increased(P<0.05),the levels of SOD and GSH-Px,and the protein levels of p-AMPK/AMPK and SIRT1 decreased(P<0.05).Compared with Model group,the number of cardiomyocytes in SY group increased and were neatly arranged,the levels of TC,TG,LDL-C,ox-LDL,IL-6,TNF-α,the apoptosis rate of cardiomyocytes,and the protein level of NF-κB decreased(P<0.05),the levels of SOD and GSH-Px,and the protein levels of p-AMPK/AMPK and SIRT1 increased(P<0.05);the above indicators in the EX-527 group showed the opposite trends.Compared with SY group,the myocardial injury in SY+EX-527 group was aggravated,the levels of TC,TG

关 键 词：冠心病 花黄色素 腺苷酸活化蛋白激酶/沉默信息调节因子1/核转录因子-κB通路 氧化应激 

分 类 号：R541.4[医药卫生—心血管疾病]