基于SIRT3/MnSOD信号通路探讨健脾调脂方对心力衰竭大鼠心肌纤维化的影响  

Effects of decoction for tonifying spleen and regulating lipid on myocardial fibrosis in ratswith heart failure via SIRT3/MnSOD signalling pathway

作　　者：王新 付蓉 覃余 高代材 WANG Xin;FU Rong;QIN Yu;GAO Daicai(Guizhou University of Traditional Chinese Medicine,Guiyang 550025,Guizhou,China;The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550001,Guizhou,China;Yanyuan County Hospital of Traditional Chinese Medicine,Yanyuan 615000,Sichuan,China)

机构地区：[1]贵州中医药大学,贵州贵阳550025 [2]贵州中医药大学第二附属医院,贵州贵阳550001 [3]盐源县中医医院,四川盐源615000

出　　处：《现代中西医结合杂志》2024年第1期48-53,59,共7页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：贵州省科技计划项目(黔科合支撑[2021]一般009)。

摘　　要：目的 基于沉默调节蛋白3/锰超氧化物歧化酶(SIRT3/MnSOD)信号通路探讨健脾调脂方改善心力衰竭心肌纤维化的机制。方法 从70只雄性SD大鼠中随机选择10只作为正常组,其余60只采用阿霉素尾静脉注射方法建立心力衰竭心肌纤维化模型。造模成功后,将存活大鼠随机分为模型组、卡托普利组、健脾调脂方低剂量组、健脾调脂方中剂量组、健脾调脂方高剂量组,每组10只。卡托普利组给予卡托普利2.6 mg/kg灌胃,健脾调脂方低、中、高剂量组分别给予健脾调脂方4.38 g/kg、8.75 g/kg、17.75 g/kg灌胃,正常组和模型组给予等体积生理盐水灌胃,均1次/d,连续6周。末次灌胃40 min后,采用心脏彩超评估心功能;取左心室心肌组织,HE及Masson染色观察病理形态及心肌纤维化情况,计算心肌胶原容积分数;Western blot法检测心肌组织中Ⅰ型胶原蛋白(CollagenⅠ)、Ⅲ型胶原蛋白(CollagenⅢ)、SIRT3及MnSOD蛋白表达情况,RT-qPCR法检测心肌组织中CollagenⅠ、CollagenⅢ、SIRT3及MnSOD mRNA表达情况。结果 模型组大鼠左心室舒张末期内径(LVIDd)、左心室收缩末期内径(LVIDs)及心肌胶原容积分数均高于正常组(P均<0.05),左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)均明显低于正常组(P均<0.05),心肌纤维断裂、出血;卡托普利组和健脾调脂方各组LVIDd、LVIDs及心肌胶原容积分数均明显低于模型组(P均<0.05),LVEF、LVFS均明显高于模型组(P均<0.05),心肌纤维化减轻,其中卡托普利组和健脾调脂方中、高剂量组减轻更明显,但仍见少量出血。模型组大鼠心肌组织中CollagenⅠ、CollagenⅢ蛋白及mRNA相对表达量均明显高于正常组(P均<0.05),SIRT3、MnSOD蛋白及mRNA相对表达量均明显低于正常组(P均<0.05);卡托普利组和健脾调脂方中、高剂量组大鼠心肌组织中CollagenⅠ、CollagenⅢ蛋白及mRNA相对表达量均明显低于模型组(P均<0.05),卡托普利组和健脾�Objective It is to explore the mechanism of decoction for tonifying spleen and regulating lipid(DTSRL)in improving myocardial fibrosis of heart failure via silent information regulator 3/manganese superoxide dismutase(SIRT3/MnSOD)signal pathway.Methods Seventy male SD rats were selected,in which 10 ones were randomly selected as the normal group,and the remaining 60 rats were given adriamycin by tail vein injection to establish models of myocardial fibrosis of heart failure.After successful modeling,the surviving rats were randomly divided into model group,captopril group,DTSRL low-dose group,DTSRL medium-dose group,and DTSRL high-dose group,with 10 rats in each group.The captopril group was given captopril 2.6 mg/kg by gavage,the low-dose,medium-dose and high-dose groups of DTSRL were given DTSRL 4.38 g/kg,8.75 g/kg and 17.75 g/kg by gavage,respectively,and the normal group and model group were given equal volumes of normal saline by gavage,all once daily,continuously treated for 6 weeks.40 minutes after the final gavage,the cardiac function was assessed by cardiac ultrasound;left ventricular myocardial tissue was taken to observe the pathological morphology and myocardial fibrosis by HE and Masson staining,and the myocardial collagen volume fraction was calculated;the expressions of CollagenⅠ,CollagenⅢ,SIRT3 and MnSOD proteins in myocardial tissue were detected by Western blot,the expressions of CollagenⅠ,CollagenⅢ,SIRT3 and MnSOD mRNAs in myocardial tissue were detected by RT-qPCR.Results The LVIDd,LVIDs and myocardial collagen volume fraction of rats in the model group were higher than those of rats in the normal group(all P<0.05),and the LVEF and LVFS were significantly lower than those in the normal group(all P<0.05),with myocardial fiber ruptures and hemorrhages;the LVIDd,LVIDs and myocardial collagen volume fraction of rats in the captopril group and every DTSRL group were lower than those of rats in the model group(all P<0.05),and the LVEF and LVFS were significantly higher than those in the mode

关 键 词：心力衰竭 心肌纤维化 健脾调脂方 沉默调节蛋白3 锰超氧化物歧化酶 

分 类 号：R-332[医药卫生]