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miRNA-124调控ERK/p38 MAPK-NLRP3通路对脓毒症心肌损伤的作用机制

The mechanism of miRNA-124 regulating the ERK/p38 MAPK-NLRP3 pathway in sepsis-induced myocardial injury
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摘要 目的 探讨miRNA-124通过调控ERK/p38 MAPK-NLRP3炎性小体通路对脓毒症心肌损伤的作用。方法 选取50只C57BL/6小鼠,随机分为正常对照组、模型组、miRNA-124敲除模型组、ERK抑制剂组和p38MAPK抑制剂组5组,每组10只。采用H&E染色评估心脏损伤,TUNEL法检测凋亡,ELISA测定炎症因子水平,Western blot分析相关蛋白表达。结果 模型组出现明显的心肌细胞浸润、水肿和坏死,伴随凋亡增加及TNF-α、IL-1β、IL-6等炎症因子升高,miRNA-124敲除加剧了这些变化;而ERK或p38MAPK抑制剂则减轻了损伤程度。结论 miRNA-124通过抑制ERK/p38 MAPK信号通路,降低Cleaved caspase-1、NLRP3、ASC的表达,从而减少脓毒症引起的心肌损伤。 Objective To investigate the effect of miRNA-124 on septic myocardial injury by regulating ERK/p38 MAPK-NLRP 3 inflammasome pathway.Methods 50 C57BL/6 mice were randomly divided into 5 groups of normal control,model,miRNA-124 knockout model,ERK inhibitor and p38MAPK inhibitor.Cardiac damage was assessed by H&.E staining,apoptosis by TUNEL,levels of inflammatory factors by ELISA,and Western blot analysis of relevant protein expression.Results In the model group,significant cardiomyocyte infiltration,edema and necrosis occurred with increased apoptosis and increased inflammatory factors such as TNF-α,IL-1βand IL-6:miRNA-124 knockout intensified and ERK or p38MAPK inhibitors reduced the damage.Conclusion miRNA-124 reduces the expression of Cleaved caspase-1,NLRP 3 and ASC by inhibiting the ERK/p38 MAPK signaling pathway,thus reducing the myocardial damage caused by sepsis.
作者 吴言悟 许安娜 王燊妮 林晓鸿 李秀珍 纪腾飞 WU Yanwu;XU Anna;WANG Shenni;LIN Xiaohong;LI Xiuzhen;JI Tengfei(Department of Anesthesiology,Jinjiang Traditional Chinese Medicine Hospital,Jinjiang,Fujian 362299,China)
出处 《中国实验诊断学》 2025年第5期599-606,共8页 Chinese Journal of Laboratory Diagnosis
基金 福建省泉州市科技计划项目(2022NS016)。
关键词 脓毒症 心肌损伤 微RNA 细胞外信号调节激酶 p38丝裂原激活的蛋白激酶 核苷酸结合结构域富含亮氨酸重复序列 含热蛋白结构域受体3 Sepsis Myocardial injury MicroRNA Extracellular signal-regulated kinase p38 mitogen-activated pro-tein kinase Nucleotide-binding domain leucine-rich repeat pyrin domain-containing receptor 3
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