ABSTRACT
Aim Timely re establishment of coronary blood How in patients with myocardial infarction is the cornerstone of their treatment; however, substantial amount of damage can oecur as a consequence of reperfusion.In recent years it has been found that receptor interacting protein kinase 3 ( RIPK3 ) contributes remarkably to myocardial ischemia-reperfusion injury (MIRI).RIPK3 can regulate necroptosis through RIPK1/RIPK3/MLKL and CaMKII, respectively, and participate in the MIRI process.This artiele reviews the researeh progress of RIPK3-mediated ne¬ croptosis involved in MIRI from endoplasmic reticulum stress, mitochondrial fragmentation disturbanee, cardiac microvascular dysfunction and inflammation, and focuses on whether RIPK3 can be used as a new target for anti-MIRI, so as to provide a new strategy and choice for improving the clinical treatment effect and prognosis of ischemic heart disease.
ABSTRACT
This study was to investigate the protective effects of puerarin on myocardial ischemia/reperfusion (MI/R) injury and the underlying mechanism. The MI/R-model was established by ligating the left anterior descending artery (LAD) for 60 min followed by 24 h reperfusion, puerarin (10, 30, and 100 mg·kg-1) was orally administered 20 min before reperfusion. Cardiac function, myocardial infarct index, cardiac damage markers, inflammatory cytokines, and apoptosis index were measured to evaluate the protective effects of puerarin on MI/R injury. The activation of Nod-like receptor protein 3 (NLRP3) inflammasome and Toll like receptor 4 (TLR4)/myeloid differentiation factor 88 (Myd88)/nuclear factor kappa B (NF-κB) pathway were determined by Western blot. All animal experimental procedures were approved by the ethics committee of the Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences. The results showed that puerarin could significantly improve cardiac function, reduce myocardial infarct size, decease the levels of lactic dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase-MB (CK-MB), and cardiac troponin T (cTnT) and suppress cardiomyocyte apoptosis. Meanwhile, puerarin could notably decrease the levels of inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Western blot analysis revealed that puerarin could downregulate the expression of TLR4, Myd88, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cleaved-caspase 1, cleaved-gasdermin-D (GSDMD), IL-1β, and IL-18, as well as the phosphorylation levels of inhibitor of NF-κB α (IκBα), IκB kinase β (IKKβ), and NF-κB. These findings demonstrated that puerarin could alleviate MI/R injury by suppressing NLRP3 inflammasome activation, possibly via TLR4/Myd88/NF-κB pathway.