IGF-1通过TLR4/NF-κB信号通路对心肺复苏大鼠心肌坏死性凋亡的影响  

Effect of IGF-1 on myocardial necroptosis in rats undergoing cardiopulmonary resuscitation via TLR4/NF-κB signaling pathway

作　　者：胡振飞[1] 李帆[1] 戴晓雯[1] HU Zhen-fei;LI Fan;DAI Xiao-wen(Department of Anesthesiology,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830000,China)

机构地区：[1]新疆医科大学第一附属医院麻醉科,新疆乌鲁木齐830000

出　　处：《河北医科大学学报》2024年第5期549-554,共6页Journal of Hebei Medical University

基　　金：新疆维吾尔自治区自然科学基金(2019D01C324)。

摘　　要：目的探究心肺复苏对胰岛素样生长因子1(insulin-like growth factor-1,IGF-1)的表达及其调节大鼠心肌损伤的作用机制。方法取30只Sprague-Dawley大鼠,随机平均分为5组,每组6只。随机选取1组为sham组,其余4组大鼠构建心室颤动型心脏骤停/心肺复苏模型,建模成功后,随机选取1组作为CA/CPR,剩余3组分为补充IGF-1、补充TAK-242[Toll样受体4(Toll-like receptor 4,TLR4)/核因子κB(nuclear factorκB,NF-κB)通路]抑制剂以及同时补充IGF-1和TAK-242组。利用伊文思蓝染色检测不同处理组大鼠的心肌损伤情况;利用实时荧光定量逆转录聚合酶链反应(reverse transcription-polymerase chain reaction,RT-qPCR)检测IGF-1的表达水平;利用Western blot检测TLR4、NF-κB、髓样分化因子(myeloid differentiation primary response protein 88,MyD88)、受体相互作用蛋白激酶3(receptor-interacting protein kinase 3,RIPK3)、混合谱系激酶域样蛋白(mixed-lineage kinase domain-like,MLKL)的表达水平;利用酶联免疫吸附法检测白细胞介素1β(interleukin-18,IL-1β)和白细胞介素18(interleukin-18,IL-18)的表达水平。结果与sham组相比,当大鼠心脏骤停后,利用心肺复苏恢复心脏自主循环后,大鼠的心肌组织均出现较为严重的损伤,其中CA/CPR组损伤严重,补充IGF-1和TAK-242组心肌损伤减轻;与sham组相比,CA/CPR组大鼠心肌细胞IGF-1的表达量显著降低(P<0.05);与sham组相比,CA/CPR大鼠心肌组织中IL-1β和IL-18的表达水平显著升高,补充IGF-1和TAK-242组大鼠在所有模型大鼠中IL-1β和IL-18的表达量最低(P<0.05);与sham组相比,CA/CPR大鼠TLR4、MyD88、NF-κB p65的表达水平显著升高,其中模型组大鼠在所有模型大鼠中的表达水平最高,补充IGF-1和TAK-242组大鼠在所有模型大鼠中的表达水平显著降低(P<0.05);与sham组相比,CA/CPR大鼠RIPK3、MLKL的表达量显著升高,补充IGF-1和TAK-242组大鼠在所有CA/CPR大鼠中的表达水平降低(P<0.05)。结论心脏骤Objective To explore the effect of cardiopulmonary resuscitation(CPR)on the expression of insulin-like growth factor-1(IGF-1)and its regulatory mechanism on myocardial injury in rats.Methods Thirty Sprague-Dawley rats were selected and randomly divided into five groups,with 6 rats in each group.One group was randomly selected as sham operation group,and in the other four groups,cardiac arrest due to ventricular fibrillation/CPR models were established.After the successful modeling,one group was randomly selected as I/R,and the other three groups were divided into IGF-1 supplementation group,TAK-242[Toll-like receptor 4(TLR4)/nuclear factorκB(NF-κB)supplementation]inhibitor supplementation group and IGF-1 and TAK-242 supplementation group.The myocardial injury of rats in different treatment groups was detected by Evans blue staining.The expression level of IGF-1 was detected by real-time fluorescence quantitative reverse transcription-polymerase chain reaction(RT-qPCR).The expression levels of TLR4,NF-κB,myeloid differentiation primary response protein 88(MyD88),receptor-interacting protein kinase 3(RIPK3)and mixed-lineage kinase domain-like(MLKL)were detected by Western blot.The expression levels of interleukin-1β(IL-1β)and interleukin-18(IL-18)were detected by enzyme-linked immunosorbent assay(ELISA).Results Compared with the sham operation group,the myocardial tissue of rats was seriously damaged after cardiac arrest and CPR,among which the model group had the most severe damage,and the IGF-1 and TAK-242 supplementation group had the least severe damage.Compared with sham operation group,the expression of IGF-1 in myocardial tissue of rats in model group was decreased significantly(P<0.05).Compared with sham operation group,the expression levels of IL-1βand IL-18 in myocardial tissue of model rats were significantly increased,among which the expression levels of IL-1βand IL-18 were the highest in the model group and the lowest in IGF-1 and TAK-242 supplementation group(P<0.05).Compared with sham operatio

关 键 词：肌细胞 心脏 心肺复苏 坏死性凋亡 

分 类 号：R542.2[医药卫生—心血管疾病]