摘要
目的分析青蒿素对心肌梗死(MI)模型大鼠心肌损伤标志物及Toll-样受体4/髓样分化蛋白抗原88/核因子κB(TLR4/MyD88/NF-κB p65)信号通路的影响。方法将70只SD大鼠随机分为假手术组、模型组和青蒿素低、中、高剂量组(20mg/kg、40mg/kg、80mg/kg,灌胃4周)各12只,采用冠状动脉结扎法复制大鼠MI模型。药物干预后,HE染色和TUNEL染色检测各组大鼠心肌组织损伤,化学发光免疫标记法检测血清肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、心肌肌钙蛋白I(cTnI)水平,ELISA法测定血清白介素6(IL-6)、IL-10和肿瘤坏死因子α(TNF-α)水平,Western Blot检测心肌组织TLR4、MyD88、NF-κB p65、磷酸化的NF-κB抑制蛋白(p-IκB)和裂解的天冬氨酸特异性半胱氨酸蛋白酶(cleaved Caspase)-3表达。结果与假手术组比较,模型组大鼠血清CK-MB、LDH、cTnI、IL-6、IL-10、TNF-α水平明显升高(P<0.05),心肌组织TLR4、MyD88、NF-κB p65、p-IκB和cleaved Caspase-3表达明显升高(P<0.05),心肌组织细胞凋亡率明显升高(P<0.05);与模型组比较,青蒿素高、中剂量组大鼠血清CK-MB、LDH、cTnI、IL-6、TNF-α水平明显下降(P <0.05),IL-10水平明显升高(P <0.05),心肌组织TLR4、MyD88、NF-κB p65、p-IκB和cleaved Caspase-3表达明显下降(P<0.05),心肌组织细胞凋亡率明显降低(P<0.05),以上差异均有统计学意义。结论青蒿素可能通过抑制TLR4/MyD88/NF-κB p65信号通路,抑制炎症因子的释放,减轻心肌组织损伤。
Objective To analyze the effects of artemisinin on myocardial injury markers and Toll-like receptor 4/myeloid differentiation protein 88/nuclear factor κB p65(TLR4/MyD88/NF-κB p65) signaling pathway in rats with myocardial infarction(MI).Methods Seventy SD rats were randomly divided into sham operation group, model group, low-dose, medium-dose and high-dose artemisinin groups(20,40,80 mg/kg, gavage for 4 weeks),12 cases in each group.MIrats models were replicated by coronary artery ligation method.After drug intervention, myocardial tissues injury in each group was detected by HE staining and TUNEL staining.The levels of serum creatine kinase MB(CK-MB),lactate dehydrogenase(LDH) and cardiac troponin I(cTnI) were detected by Chemiluminescence immunolabeling method.The levels of serum interleukin 6(IL-6),IL-10 and tumor necrosis factor α(TNF-α) were detected by ELISA.The expression of TLR4,MyD88,NF-κB p65,phosphorylated NF-κB inhibitor protein(p-IκB) and cleaved cysteinyl aspartate specific proteinase(cleaved Caspase)-3 in myocardial tissues was detected by Western Blot.Results Compared with sham operation group, levels of serum CK-MB,LDH,cTnI,IL-6,IL-10 and TNF-α were significantly increased in model group(P<0.05),expression of TLR4,MyD88,NF-κB p65,p-IκB and cleaved Caspase-3 in myocardial tissues was significantly increased(P<0.05),and apoptosisrate of myocardial tissueswas significantly increased(P<0.05).Compared with model group, levels of serum CK-MB,LDH,cTnI,IL-6 and TNF-α were significantly decreased in medium-dose and high-dose artemisinin groups(P<0.05),IL-10 level was significantly increased(P<0.05),expression of TLR4,MyD88,NF-κB p65,p-IκB and cleaved Caspase-3 in myocardial tissues was significantly decreased(P<0.05),and apoptosisrate of myocardial tissues was significantly decreased(P<0.05),the above differences were statistically significant.Conclusion Artemisinin may inhibit the release of inflammatory factors and reduce myocardial tissue injury by inhibiting TLR4/MyD88/NF-κB p65 signali
作者
李亚云
宗刚军
黄月皎
LI Yayun;ZONG Gangjun;HUANG Yuejiao(Department of General Internal Medicine,Nantong Tumor Hospital,Nantong 226006,China)
出处
《中国煤炭工业医学杂志》
2021年第3期225-230,共6页
Chinese Journal of Coal Industry Medicine
基金
国家自然科学青年基金(编号:81600158)。
