Leonurine improve necrotic apoptosis in rats with myocardial ischemia/reperfusion injury by regulating RIP1-RIP3-MLKL pathway
10.3969/j.issn.1000-484X.2025.08.014
- VernacularTitle:益母草碱通过调节RIP1-RIP3-MLKL通路改善心肌缺血/再灌注损伤大鼠坏死性凋亡
- Author:
Mingfang LI
1
;
Bibo TANG
;
Caijin YANG
;
Chaoquan LIU
Author Information
1. 海南西部中心医院儿科,儋州 571700
- Publication Type:Journal Article
- Keywords:
Leonurine;
RIP1-RIP3-MLKL pathway;
Myocardial ischemia/reperfusion;
Necrotic apoptosis
- From:
Chinese Journal of Immunology
2025;41(8):1879-1884
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate impact of leonurine(Leo)on necrotic apoptosis in rats with myocardial ischemia/reperfu-sion(MIR)injury by regulating receptor interacting protein 1(RIP1)-receptor interacting protein 3(RIP3)-mixed lineage kinase domain-like protein(MLKL)pathway.Methods:Fifteen rats were randomly selected as sham surgery group(Sham),left anterior descending coronary artery of remaining rats were ligated to construct MIR model,and randomly grouped into MIR group,Leo group(15 mg/kg),Compound 6i group(1 mg/kg RIP1-RIP3-MLKL pathway activator Compound 6i)and Leo+Compound 6i group(15 mg/kg Leo+1 mg/kg Compound 6i),with 15 rats in each group.MIR group and Sham group were injected with equal amounts of physiological saline.Cardiac function indicators were observed through ultrasound electrocardiogram;ELISA was applied to detect myocardial injury indicators and inflammatory factor levels;HE staining was applied to observe pathological damage of heart;TTC staining was applied to detect myocardial infarction area;TUNEL staining was applied to detect cell apoptosis;Western blot was applied to detect expres-sions of RIP1-RIP3-MLKL pathway proteins.Results:Myocardial cells in Sham group were intact and arranged in an orderly manner;arrangement of myocardial cells was disordered and swollen,myofibril contracted,and sarcolemma was destroyed in MIR group,ejec-tion fraction(EF)and cardiac output(CO)level were obviously lower than Sham group(P<0.05),Mb,cTnⅠ,CK-Mb contents,IL-6,IL-18 levels,myocardial infarction area,myocardial cell apoptosis rate,RIP1,RIP3 and MLKL protein levels were obviously increased(P<0.05);compared with MIR group,Leo group had improved cell arrangement disorder and edema,and obviously increased EF and CO levels(P<0.05),Mb,cTnⅠ,CK-Mb contents,IL-6,IL-18 levels,myocardial infarction area,myocardial cell apoptosis rate,RIP1,RIP3 and MLKL protein levels were obviously reduced(P<0.05),trend of Compound 6i group was opposite;myocardial tissue structure of Leo+Compound 6i group was similar to MIR group,and Compound 6i eliminated cardioprotective effect of Leo on MIR rats.Conclusion:Leo may alleviate myocardial necrosis apoptosis in MIR rats by down-regulating RIP1-RIP3-MLKL pathway,thus playing a therapeutic role in MIR.
