您的位置：山东大学 -> 科技期刊社 -> 《山东大学学报（医学版）》

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

PDF (PC)

354

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
[1] Pauschinger M, Noutsias M, Lassner D, et al. Inflammation, ECG changes and pericardial effusion: whom to biopsy in suspected myocarditis[J]. Clin Res Cardiol, 2006, 95(11): 569-583.
[2] Lazzerini PE, Capecchi PL, Laghi-Pasini F. Statins as a new therapeutic perspective in myocarditis and postmyocarditis dilated cardiomyopathy: editorial to "pitavastatin regulates helper T-cell differentiation and ameliorates autoimmune myocarditis in mice" by K Tajiri et al[J]. Cardiovasc Drugs Ther, 2013, 27(5): 365-369.
[3] Kong Q, Wu W, Yang F, et al. Increased expressions of IL-22 and Th22 cells in the coxsackievirus B3-Induced mice acute viral myocarditis[J]. Virol J, 2012, 9(1): 232-241.
[4] Chang H, Hanawa H, Liu H, et al. Hydrodynamic-based delivery of an interleukin-22-Ig fusion gene ameliorates experimental autoimmune myocarditis in rats[J]. J Immunol, 2006, 177(6): 3635-3643.
[5] 王介忠, 韩波, 高聆, 等. CD40 siRNA对EAM大鼠的作用及其对 CD4+CD25+Treg的影响[J]. 山东大学学报: 医学版, 2014, 52(1): 1-4. WANG Jiezhong, HAN Bo, GAO Ling, et al. Effect of CD40 siRNA on CD4+CD25+ regulatory T cells in rats with experimental autoimmune myocarditis[J]. Journal of Shandong University: Health Sciences, 2014, 52(1): 1-4.
[6] 杨文巍, 韩波, 王介忠, 等. CD40 siRNA对实验性自身免疫性心肌炎大鼠Th17细胞及其细胞因子白细胞介素-17与白细胞介素-23的作用[J]. 中华实用儿科临床杂志, 2013, 28(19): 1498-1501. YANG Wenwei, HAN Bo, WANG Jiezhong, et al. Effect of CD40 siRNA on T helper lymphocyte-17 cells and interleukin-17, interleukin-23 in rats with experimental autoimmune myocarditis[J]. Chin J Appl Clin Pediatr, 2013, 28(19): 1498-1501.
[7] Rezkalla S, Kloner RA, Khatib G, et al. Effect of metoprolol in acute COX-sackievirus B3 murine myocarditis[J]. J Am Coll Cardiol, 1988, 12 (2): 412-414.
[8] Reddy J, Massilamany C, Buskiewicz I, et al. Autoimmunity in viral myocarditis[J]. Curr Opin Rheumatol, 2013, 25(4): 502-508.
[9] Caforio AL, Pankuweit S, Arbustini E, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases[J]. Eur Heart J, 2013, 34(33): 2636-2648.
[10] Sato Y, Fujiwara H, Takatsu Y. Cardiac troponin and heart failure in the era of high-sensitivity assays[J]. J Cardiol, 2012, 60(3): 160-167.
[11] Nakagawa O, Ogawa Y, Itoh H, et al. Rapid transcriptional activation and early mRNA turnover of BNP in cardiocyte hypertrophy: evidence for BNP as an “emergency” cardiac hormone against ventricular overload[J]. J Clin Invest, 1995, 96(3): 1280-1287.
[12] Kim CJ, Nazli A, Rojas OL, et al. A role for mucosal IL-22 production and Th22 cells in HIV-associated mucosal immunopathogenesis[J]. Mucosal Immunol, 2012, 5(6): 670-680.
[13] Wan Q, Kozhaya L, ElHed A, et al. Cytokine signals through PI-3 kinase pathway modulate Th17 cytokine production by CCR6+ human memory T cells[J]. J Exp Med, 2011, 208(9): 1875-1887.
[14] Mitra A, Raychaudhuri SK, Raychaudhuri SP. IL-22 induced cell proliferation is regulated by PI3K/Akt/mTOR signaling cascade[J]. Cytokine, 2012, 60(1): 38-42.
[15] Zhang L, Li YG, Li YH, et al. Increased frequencies of Th22 cells as well as Th17 cells in the peripheral blood of patients with ankylosing spondylitis and rheumatoid arthritis[J]. PLoS One, 2012, 7(4): 31000.
[16] Truchetet ME, Brembilla NC, Montanari E, et al. Increased frequency of circulating Th22 in addition to Th17 and Th2 lymphocytes in systemic sclerosis: association with interstitial lung disease[J]. Arthritis Res Ther, 2011, 13(5): 166.
[17] Ikeuchi H, Kuroiwa T, Hiramatsu N, et al. Expression of interleukin-22 in rheumatoid arthritis: potential role as a proinflammatory cytokine[J]. Arthritis Rheum, 2005, 52(4): 1037-1046.
[18] Radaeva S, Sun R, Pan HN, et al. Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation[J]. Hepatology, 2004, 39(5): 1332-1342.
[19] Whittington HA, Armstrong L, Uppington KM, et al. Interleukin-22: a potential immunomodulatory molecule in the lung[J]. Am J Respir Cell Mol Biol, 2004, 31(2): 220-226.
[1] 吴逸南 葛志明 李方 贺红 姜虹 张运. 自发性高血压大鼠肾脏血管紧张素转换酶2的表达[J]. 山东大学学报(医学版), 2209, 47(6): 5-.
[2] 祝林 胡三元 张光永 丁祥就. 前列腺素E2对阻塞性黄疸大鼠小肠粘膜形态的保护作用[J]. 山东大学学报(医学版), 2209, 47(6): 12-.
[3] 孙涛 张道来 谢珊珊 王玉卓 冯玉新 辛华. 酒精对原代培养的神经前体细胞间隙连接蛋白43表达的影响[J]. 山东大学学报(医学版), 2209, 47(6): 20-.
[4] 张道来 孙涛 谢珊珊 王玉卓 赵玲 冯玉新 辛华. 体外原代培养胎鼠大脑皮层神经元NMDAR1亚基表达的发育性变化[J]. 山东大学学报(医学版), 2209, 47(6): 28-32.
[5] 赵子辉,王旭阳,张鹏,方宁宁,石端博,杨帆,杨晓玫,吴剑波. 经膈肌穿刺法快速准确评估大鼠肺动脉高压[J]. 山东大学学报 (医学版), 2024, 62(2): 20-28.
[6] 祁少俊,唐延金,张正铎,吴虹,张佳程,秦川,刘锐,高希宝. 补充多种微量元素对高糖饮食大鼠的保护作用[J]. 山东大学学报 (医学版), 2023, 61(7): 19-26.
[7] 虎娜,孙苗,邢莎莎,许丹霞,海小明,马玲,杨丽,勉昱琛,何瑞,陈冬梅,马会明. 月见草油抵抗多囊卵巢综合征大鼠卵巢氧化应激[J]. 山东大学学报 (医学版), 2022, 60(5): 22-30.
[8] 张正铎,吴虹,祁少俊,唐延金,高希宝. 口服5-甲基四氢叶酸对大鼠阿尔茨海默病的预防作用[J]. 山东大学学报 (医学版), 2022, 60(3): 13-23.
[9] 赵慧文,许琳,单姗,赵秀兰. 牛磺酸对1-溴丙烷致大鼠认知功能障碍的保护作用[J]. 山东大学学报 (医学版), 2022, 60(2): 14-21.
[10] 郭曼,刘鹏,龙麟. 防纤汤对放射性肺炎大鼠的影响及作用机制[J]. 山东大学学报 (医学版), 2021, 59(8): 53-60.
[11] 南莉,杨凯转,张一帆. 室内照明白色发光二极管对大鼠视网膜的影响[J]. 山东大学学报 (医学版), 2021, 59(4): 56-62.
[12] 王海鹏,邹娟娟,高春苗,王孝,王岩,李延忠. OSAHS慢性间歇性低氧大鼠模型的建立及意义[J]. 山东大学学报 (医学版), 2021, 59(2): 7-13.
[13] 张霁娟,于汉成,王蓝,陈诺,崔书萌,高希宝. 高脂膳食、硒对大鼠抗氧化功能的影响[J]. 山东大学学报 (医学版), 2021, 59(1): 95-101.
[14] 何天齐,李敏,王雪楠,王亚楠,李玉川,孙爽,赵海龙,王皓,陈大典,朱梅佳,王晓军,王敏,李秀华. 腺相关病毒在大鼠丘脑纹状体通路中的应用[J]. 山东大学学报 (医学版), 2020, 58(3): 65-74.
[15] 丁华琳,李扬扬,于丰源,战伟伟,于苏国. 达格列净通过Klotho/TGF-β1通路抑制糖尿病肾病大鼠肾纤维化的作用[J]. 山东大学学报 (医学版), 2020, 58(3): 75-80.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
版权所有 © 2018 《山东大学学报(医学版)》编辑部　
地址:山东大学科技期刊社（济南市历城区山大南路27号山东大学中心校区明德楼B座721室） 电话: 0531-88366918 E-mail: xbyxb@sdu.edu.cn
本系统由北京玛格泰克科技发展有限公司设计开发