论文部分内容阅读
目的：探讨小分子干扰 RNA（siRNA）沉默 CD40基因表达后对实验性自身免疫性心肌炎（EAM）大鼠心肌组织病理变化、血清肌钙蛋白 T（cTNT）、脑钠肽（BNP）及白细胞介素-22（IL-22）的影响及意义。方法将6～8周雄性 Lewis 大鼠48只随机分为正常对照组、EAM 组、CD40 siRNA 组及 siRNA 组，每组12只。在免疫第21天，每组处死6只大鼠，免疫第56天，处死剩余全部大鼠，光镜与电镜下观察大鼠心肌组织病理及超微结构的改变，计算心肌组织病理积分，酶联免疫吸附试验（ELISA）检测血清 cTNT、BNP 及 IL-22的浓度。结果免疫第21天与第56天，除正常对照组，其他3组大鼠发病率均为100％。各组大鼠生存率与死亡率无差异（P ＞0．05）；CD40 siRNA 组心肌组织病理积分、cTNT 和 BNP 的水平均明显低于 EAM组（P ＜0．05），IL-22的水平均明显高于 EAM组（P ＜0．05），且cTNT和 BNP 均与心肌组织病理积分呈正相关性（r ＝0．732，r ＝0．869，P ＜0．05）。结论siRNA 沉默 CD40基因表达能减轻 EAM大鼠心肌炎症，降低心肌损伤程度，改善心功能，其机制可能与上调 IL-22的表达，抑制免疫反应有关。“,”Objective To explore the effects of CD40 knockdown by siRNA on myocardial tissues,cTNT,BNP and IL-22 in rats with experimental autoimmune myocarditis (EAM).Methods A total of 48 male Lewis rats aged 6-8 weeks were randomly divided into normal control group,EAM group,CD40 siRNA group and siRNA group,with 12 rats in each group.On day 21,6 rats were sacrificed respectively in each group;on day 56,the remaining rats were killed.The histopathologic and ultrastructure changes were observed with light and electron microscope.The myocardial histopathologic scores were counted,and cTNT,BNP and IL-22 were tested with ELISA.Results On day 21 and 56, the total incidence rate of each group was 100% except the normal control group,and there was no statistical difference in survival rate and mortality rate in each group (P >0.05).Myocardial histopathological scores,serum levels of cTNT and BNP in CD40 siRNA group were significantly lower than those in EAM group (P <0.05),while the serum level of IL-22 was higher than that in EAM group (P <0.05),and the serum levels of cTNT and BNP were positively corre-lated with myocardial histopathological scores (r =0.732,r =0.869,P <0.05).Conclusion Silencing CD40 by siRNA can relieve inflammation in EAM,alleviate myocardial injury and improve heart function.The mechanism may involve the up-regulation of IL-22 expression and inhibition of immune response.