炎症因子在大鼠冠状动脉微栓塞后心肌组织中的表达及NF-κB抑制剂对其的影响

Expression of inflammatory factors in myocardium following coronary microembolization and effect of NF-κB inhibitor on the expression in rats

目的探讨炎症因子在冠状动脉微栓塞(CME)后心肌组织中的表达及核因子(B(NF-κB)抑制剂的干预作用。方法清洁级雄性SD大鼠88只,其中64只经左心室内注射自体微血栓、同时短暂夹闭主动脉建立大鼠CME模型后,随机分为未治疗组及NF-κB抑制剂二硫代氨基甲酸吡咯烷(PDTC)干预组,分别于术后1、3、7、14 d处死;余24只为假手术组。原位杂交及免疫组织化学染色检测肿瘤坏死因子α(TNF-α)、白介素6(IL-6)及细胞间黏附因子1(ICAM-1)等炎症因子在心肌中的空间分布及动态变化。结果 CME炎症并不仅局限于微梗灶及周围,同时波及到许多"无辜心肌",产生"旁观者效应"。CME组在不同观察时间点心肌TNF-α、IL-6、ICAM-1蛋白的表达较假手术组均明显增强(P<0.05)。NF-κB特异性抑制剂PDTC干预能抑制CME后心肌中TNF-α、IL-6及ICAM-1蛋白表达(P均<0.05)。结论 CME后伴发放大炎症反应,NF-κB抑制剂显著抑制心肌炎症反应。

Objective To investigate the expression of inflammatory factors in myocardium following coronary microembolization（CME） and effect of NF-κB inhibitor on the expression.Methods CME models were created in 64 rats by injecting homologous microthrombotic particle suspension into the left ventricle with the ascending aorta clamped.The model rats were equally divided into untreated group and pyrrolidine dithiocarbamate（PDTC） treatment group;the animals were sacrificed at 1,3,7,and 14 days after operation.Another 24 SD rats served as sham controls.The distribution and dynamic changes of TNF-α,IL-6 and ICAM-1 mRNA expression in myocardium were determined by in situ hybridization and immunohistochemistry.Results CME associated inflammation was not limited to the surroundings of the microembolization;it also involved a great deal of ＂innocent＂ myocardium,producing bystander effect.Myocardium expression of TNF-α,IL-6,and ICAM-1 in CME group was significantly higher than that in the sham control group（P0.05）.NF-κB inhibitor PDTC significantly inhibited TNF-α,IL-6 and ICAM-1 expression after CME（P0.05）.Conclusion CME can produce amplified myocardial inflammation,and NF-κB inhibitor PDTC can markedly ameliorate myocardial inflammation.