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山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (5): 36-40.doi: 10.6040/j.issn.1671-7554.0.2014.929

• 基础医学 • 上一篇    下一篇

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

张荣军1, 韩波1, 高聆2, 朱梅3, 丁国玉1, 梁燕1   

  1. 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
  • 收稿日期:2014-12-09 修回日期:2015-03-18 出版日期:2015-05-10 发布日期:2015-05-10
  • 通讯作者: 韩波。E-mail:hanbo35@163.com E-mail:hanbo35@163.com
  • 基金资助:
    山东省自然科学基金(ZR2011HM029);济南市科技计划项目(201401262)

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

ZHANG Rongjun1, HAN Bo1, GAO Ling2, ZHU Mei3, DING Guoyu1, LIANG Yan1   

  1. 1. Department of Pediatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China;
    2. Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China;
    3. Department of Ultrasonography, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China
  • Received:2014-12-09 Revised:2015-03-18 Online:2015-05-10 Published:2015-05-10

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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、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。

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

Abstract: 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 correlated 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.

Key words: Rats, Brain natriuretic peptide, CD40 siRNA, Autoimmune myocarditis, Cardiac troponin, Interleukin-22

中图分类号: 

  • R542.2
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