中国病理生理杂志2025，Vol.41Issue(12)：2307-2313,7.DOI:10.3969/j.issn.1000-4718.2025.12.003
RIPK1/RIPK3/MLKL通路介导的坏死性凋亡促进大鼠冠状动脉微栓塞所致心肌损伤
RIPK1/RIPK3/MLKL pathway-mediated necroptosis promotes coronary microembolization-induced myocardial injury in rats
摘要
Abstract
AIM:To investigate the mechanism by which receptor-interacting protein kinase 1(RIPK1)/RIPK3/mixed lineage kinase domain-like protein(MLKL)pathway-mediated necroptosis promotes myocardial injury in-duced by coronary microembolization(CME)in rats.METHODS:A total of 24 rats were randomly assigned to three groups(n=8 per group):sham group,CME group,and necrostatin-1(Nec-1;a necroptosis inhibitor)group.Cardiac function was assessed using echocardiography.Myocardial pathological alterations were examined by HE staining.Micro-infarct size was determined using Heidenhain staining.Ultrastructural changes in rat cardiomyocytes were observed by transmission electron microscopy.Serum levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and cardiac troponin T(cTnT)were measured by ELISA.The expression levels of the proteins associated with RIPK1/RIPK3/MLKL pathway in myocardial tissues were detected by Western blot.RESULTS:Compared with sham group,the cardiac func-tion in CME group significantly decreased,and serum cTnT level significantly increased(P<0.05).In CME group,the myocardial tissue exhibited loosely arranged fibres,partial nuclear fragmentation,and karyolysis in some cells.The myo-cardial mitochondria showed swelling and vacuolization,with cristae rupture or even disappearance,and the myocardial microinfarction area increased significantly(P<0.05).Moreover,the expression of inflammatory factors IL-1β and TNF-α significantly increased,and the p-RIPK1/RIPK1,p-RIPK3/RIPK3,and p-MLKL/MLKL protein ratios markedly in-creased(P<0.05).Compared with CME group,the rats in Nec-1 group had significantly improved cardiac function,re-duced serum cTnT level,decreased myocardial microinfarction area,and suppressed serum secretion of IL-1β and TNF-α(P<0.05).Furthermore,following Nec-1 intervention,the protein ratios of p-RIPK1/RIPK1,p-RIPK3/RIPK3 and p-MLKL/MLKL were significantly decreased(P<0.05).CONCLUSION:The RIPK1/RIPK3/MLKL signaling pathway may be involved in the pathological progression of CME in rats through the mediation of cardiomyocyte necroptosis.The in-hibition of this signaling pathway can significantly enhance cardiac function in rats,decrease the area of microinfarction,and mitigate myocardial inflammation.关键词
冠状动脉微栓塞/坏死性凋亡/心肌损伤/RIPK1/RIPK3/MLKL通路Key words
coronary microembolization/necroptosis/myocardial injury/RIPK1/RIPK3/MLKL pathway分类
医药卫生引用本文复制引用
刘阳春,杨华锋,黄源,苏强,黄万众..RIPK1/RIPK3/MLKL通路介导的坏死性凋亡促进大鼠冠状动脉微栓塞所致心肌损伤[J].中国病理生理杂志,2025,41(12):2307-2313,7.基金项目
国家自然科学基金资助项目(No.82260072 （）
No.82300376) （）
广西自然科学基金区域高发疾病研究联合专项资助(No.2024GXNSFBA010082) （No.2024GXNSFBA010082）
