茯苓多糖调节Nrf2/HO-1信号通路对大鼠心肌缺血再灌注损伤的影响  

Effect of poria cocos polysaccharides on myocardial ischemia-reperfusion injury in rats via regulating Nrf2/HO-1 signaling pathway

作　　者：安伟乔[1] 霍楠[1] 康凯宁[1] 韩越[2] 李书瑞[1] 李岩 AN Weiqiao;HUO Nan;KANG Kaining;HAN Yue;LI Shurui;LI Yan(Handan Central Hospital,Handan 056008,Hebei,China;The First Affiliated Hospital of Harbin Medical University,Haerbin 150000,Heilongjiang,China)

机构地区：[1]邯郸市中心医院,河北邯郸056008 [2]哈尔滨医科大学第一附属医院,黑龙江哈尔滨150000

出　　处：《现代中西医结合杂志》2024年第19期2634-2642,共9页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：河北省医学科学研究课题计划项目(20240788)。

摘　　要：目的探讨茯苓多糖调节核因子E2相关因子2(Nrf2)/血红素加氧酶1(HO-1)信号通路对大鼠心肌缺血再灌注损伤(MIRI)的影响。方法随机取130只清洁级SD大鼠中的24只作为假手术组,剩余106只通过阻断左冠状动脉前降支30 min方法建立MIRI模型。将96只成模大鼠随机分为模型组、茯苓多糖组、茯苓多糖+Nrf2激动剂组和茯苓多糖+Nrf2抑制剂组,每组24只。茯苓多糖组给予茯苓多糖口服液3 mL/kg灌胃和生理盐水腹腔注射,茯苓多糖+Nrf2激动剂组给予茯苓多糖口服液3 mL/kg灌胃和TBHQ 20 mg/kg腹腔注射,茯苓多糖+Nrf2抑制剂组给予茯苓多糖口服液3 mL/kg灌胃和ML38530 mg/kg腹腔注射,假手术组和模型组给予生理盐水灌胃和腹腔注射,均1次/d,连续干预4周。通过超声心动图考察大鼠心功能[左心室射血分数(LVEF)、左心室内压最大上升/下降速率(+dp/dtmax、-dp/dtmax)],TTC染色观察心肌梗死情况并计算梗死体积,HE染色观察心肌组织病理形态,TUNEL染色观察心肌细胞凋亡情况,ELISA法检测血清心肌酶[乳酸脱氢酶(LDH)、心肌肌钙蛋白I(cTnI)、肌红蛋白(Mb)、肌酸激酶同工酶(CK-MB)]水平和心肌组织中氧化应激指标[丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)]、炎症因子[白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)]含量,Western blot法检测心肌组织中Nrf2、HO-1、核因子-κB p65(NF-κB p65)和细胞凋亡相关蛋白[半胱氨酸蛋白酶-3(Caspase-3)、裂解Caspase-3(cleaved Caspase-3)、B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)]表达情况,RT-PCR法检测心肌组织中Nrf2、HO-1 mRNA表达情况。结果与模型组比较,茯苓多糖组和茯苓多糖+Nrf2激动剂组大鼠LVEF、+dp/dtmax、-dp/dtmax均明显升高(P<0.05);心肌组织梗死体积、心肌细胞凋亡率和血清LDH、cTnI、Mb、CK-MB水平均明显降低(P均<0.05),心肌组织病理变化明显减轻;心肌组织中MDA、IL-1β、Objective It is to investigate the effect of poria cocos polysaccharides(PCP)on myocardial ischemia-reperfusion injury(MIRI)in rats via regulating the nuclear factor E2 related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.Methods One hundred and thirty clean grade SD rats were randomly selected,in which 24 rats were selected as sham operation group,and the remaining 106 rats were used to establish MIRI models through blocking anterior descending branch of left coronary artery for 30 min.96 successfully modeled rats were randomly divided into model group,PCP group,PCP+Nrf2 agonist group and PCP+Nrf2 inhibitor group,with 24 rats in each group.The PCP group was given PCP oral solution 3 mL/kg by gavage and normal saline by intraperitoneal injection,the PCP+Nrf2 agonist group was given PCP oral solution 3 mL/kg by gavage and TBHQ 20 mg/kg by intraperitoneal injection,the PCP+Nrf2 inhibitor group was given PCP oral solution 3 mL/kg by gavage and ML38530 mg/kg by intraperitoneal injection,and the sham operation group and model group were given normal saline by gavage and intraperitoneal injection,all once daily,continuously treated for 4 weeks.The cardiac function[left ventricular ejection fraction(LVEF),maximum rate of increase/decrease of LV internal pressure(+dp/dtmax,-dp/dtmax)]of the rats was examined by echocardiography,myocardial infarction was observed by TTC staining and the infarct volume was calculated,myocardial histopathologic morphology was observed by HE staining,myocardial apoptosis was observed by TUNEL staining,and serum levels of myocardial enzymes[lactate dehydrogenase(LDH),cardiac troponin I(cTnI),myoglobin(Mb),creatine kinase isoenzyme(CK-MB)]and the contents of myocardial tissue oxidative stress indexes[malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT)],inflammatory factors[interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)]were measured by ELISA,the protein expressions of Nrf2,HO-1,nuclear factor-κB p65(NF-κB p65),apoptosis related proteins(Caspas

关 键 词：心肌缺血再灌注损伤 茯苓多糖 氧化应激 炎症 凋亡 核因子E2相关因子2 血红素加氧酶1 

分 类 号：R-332[医药卫生]