鲁斯可皂苷元调节SIRT3/PPARγ信号通路对急性心肌梗死后心力衰竭小鼠的心肌保护作用OA
The Cardioprotective Effect of Ruscogenin on Mice with Heart Failure after Acute Myocardial Infarction by Regulating the SIRT3/PPARγ Signaling Pathway
目的:探讨鲁斯可皂苷元(RUS)调节沉默信息调节因子3(SIRT3)/过氧化物酶体增殖物激活受体γ(PPARγ)信号通路对急性心肌梗死后心力衰竭(HF)小鼠的心肌保护作用.方法:建立急性心肌梗死后HF小鼠模型,将构建成功的小鼠随机分为HF组、RUS低剂量组、RUS高剂量组、3-TYP组(RUS高剂量+SIRT3/PPARγ信号通路抑制剂3-TYP),另外随机选取10只小鼠为Con组.检测小鼠心功能相关指标;检测小鼠血清心肌标记物、炎性和氧化应激相关因子水平;观察小鼠心肌组织病理和纤维化改变;检测小鼠心肌细胞凋亡率;Western blot检测心肌组织SIRT3/PPARγ信号通路及凋亡相关蛋白表达.结果:HF组与Con组比较,小鼠心肌组织病理损伤和纤维化严重,大量炎性细胞浸润,心肌细胞坏死,左室射血分数(LVEF)、左室短轴缩短率(LVFS)、SOD、Bcl-2、SIRT3、PPARγ表达减少,左室舒张末期容积(LVEDV)、左室收缩末期容积(LVESV)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、心肌肌钙蛋白T(cTnT)、TNF-α、IL-6、IL-8、MDA、ROS、心肌细胞凋亡率、Bax表达增加(P＜0.05);RUS低剂量组、RUS高剂量组与HF组比较,小鼠心肌组织病理损伤和纤维化改善,炎性细胞浸润和心肌细胞坏死减少,LVEF、LVFS、SOD、Bcl-2、SIRT3、PPARγ 表达增加,LVEDV、LVESV、CK-MB、LDH、cTnT、TNF-α、IL-6、IL-8、MDA、ROS、心肌 细胞凋亡率、Bax 表达减少(P＜0.05);3-TYP 组与 RUS 高剂量组比较,小鼠心肌组织病理损伤和纤维化加重,炎性细胞浸润和心肌细胞坏死增加,LVEF、LVFS、SOD、Bcl-2、SIRT3、PPARγ表达显著减少,LVEDV、LVES V、CK-MB、LDH、cTnT、TNF-α、IL-6、IL-8、MDA、ROS、心肌细胞凋亡率、Bax表达显著增加(P＜0.05).结论:RUS可能通过激活SIRT3/PPARγ信号通路,对急性心肌梗死后HF小鼠心肌起到保护作用.
Objective:To explore the cardioprotective effect of ruscogenin(RUS)on mice with heart failure(HF)after acute myocardial infarction by regulating the silent information regulator 3(SIRT3)/peroxi-some proliferator-activated receptor gamma(PPAR gamma)signaling pathway.Methods:A mouse model of HF was established after acute myocardial infarction,and successfully constructed mice were randomly separa-ted into HF group,RUS low-dose group,RUS high-dose group,and 3-TYP group(RUS high-dose+SIRT3/PPARγ signaling pathway inhibitor 3-TYP).Another 10 mice were randomly included as the Con group.Mouse heart function related indicators were detected.The myocardial markers,inflammatory and oxidative stress-related factors in mouse serum were detected.Pathological and fibrotic changes in mouse myocardial tissue were observed.The apoptosis rate of mouse myocardial cells was detected.In addition,Western blot was used to measure the SIRT3/PPARγ signaling pathway and apoptosis related protein expression in myocar-dial tissue.Results:Compared with the Con group,the HF group showed severe pathological damage and fi-brosis in mouse myocardial tissue,with a large amount of inflammatory cell infiltration,myocardial cell necro-sis,decreased left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),SOD,Bcl-2,SIRT3,and PPARγ,and raised left ventricular end diastolic volume(LVEDV),left ventricular end systolic volume(LVESV),creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH),cardiac troponin T(cTnT),TNF-α,IL-6,IL-8,MDA,ROS,myocardial cell apoptosis rate,and Bax(P＜0.05).Compared with the HF group,the low-dose RUS group and high-dose RUS group showed improved pathologi-cal damage and fibrosis of mouse myocardial tissue,reduced inflammatory cell infiltration and myocardial cell necrosis,raised LVEF,LVFS,SOD,Bcl-2,SIRT3,PPARγ,and decreased LVEDV,LVESV,CK-MB,LDH,cTnT,TNF-α,IL-6,IL-8,MDA,ROS,myocardial cell apoptosis rate,and Bax(P＜0.05).Com-pared with the high-dose RUS group,the 3-TYP group showed aggravated pathological damage and fibrosis in mouse myocardial tissue,raised inflammatory cell infiltration and myocardial cell necrosis,prominently de-creased LVEF,LVFS,SOD,Bcl-2,SIRT3,PPARγ,and prominently raised LVEDV,LVESV,CK-MB,LDH,cTnT,TNF-α,IL-6,IL-8,MDA,ROS,myocardial cell apoptosis rate,and Bax(P＜0.05).Con-clusion:RUS may have a protective effect on myocardium of mice with HF after acute myocardial infarction by activating the SIRT3/PPARγ signaling pathway.
路陆;曹程;庞文一;赵阳;卢苓苓
河北省沧州中西医结合医院,河北 沧州 061000河北省沧州中西医结合医院,河北 沧州 061000河北省沧州中西医结合医院,河北 沧州 061000河北省沧州中西医结合医院,河北 沧州 061000河北省沧州中西医结合医院,河北 沧州 061000
急性心肌梗死后心力衰竭鲁斯可皂苷元沉默信息调节因子3/过氧化物酶体增殖物激活受体γ心肌保护
Heart failure after acute myocardial infarctionRuscogeninSilent information regu-lator 3/peroxisome proliferator-activated receptor gammaMyocardial protection
《河北医学》 2026 (3)
382-389,8
河北省2025年度医学科学研究课题计划,(编号:20251568)
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