siRNA沉默CD40基因对实验性自身免疫性心肌炎大鼠的作用及IL-22表达的影响  

Effects of CD40 knockdown by siRNA on rats with experimental autoimmune myocarditis and IL-22 expression

作　　者：张荣军[1] 韩波[1] 高聆[2] 朱梅[3] 丁国玉[1] 梁燕[1] 

机构地区：[1]山东大学附属省立医院小儿心脏科,山东济南250021 [2]山东大学附属省立医院中心实验室,山东济南250021 [3]山东大学附属省立医院超声科,山东济南250021

出　　处：《山东大学学报（医学版）》2015年第5期36-40,45,共6页Journal of Shandong University:Health Sciences

基　　金：山东省自然科学基金(ZR2011HM029);济南市科技计划项目(201401262)

摘　　要：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、CD40siRNA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）；CD40siRNA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 ）. Coneluslon 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.

关 键 词：自身免疫性心肌炎 CD40小分子干扰RNA 血清肌钙蛋白T 脑钠肽 白细胞介素-22 大鼠 

分 类 号：R542.2[医药卫生—心血管疾病]