JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2015, Vol. 53 ›› Issue (5): 36-40.doi: 10.6040/j.issn.1671-7554.0.2014.929

Previous Articles     Next Articles

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

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

CLC Number: 

  • 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] ZHU Lin, HU San-Yuan, ZHANG Guang-Yong, DING Xiang-Jiu. Protection of PGE2 against intestinal mucosa injuries in obstructed jaundice rats [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 12-.
[2] SUN Tao, ZHANG Dao-Lai, XIE Shan-Shan, WANG Yu-Zhuo, FENG Yu-Xin, XIN Hua. Effect of ethanol on expression of connexin 43 in primary culture of neural precursor cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 20-.
[3] ZHANG Dao-Lai, SUN Tao, XIE Shan-Shan, WANG Yu-Zhuo, ZHAO Ling, FENG Yu-Xin, XIN Hua. Developmental expression of NMDAR1 subunit on cultured cerebral cortical neurons of fetal rats in vitro [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 28-32.
[4] ZHANG Liang, XU Min, ZHUANG Xianghua, LOU Fuchen, LOU Nengjun, LÜ Li, GUO Wenjuan, ZHENG Fengjie, CHEN Shihong. An investigation of endoplasmic reticulum stress and apoptosis in diabetic peripheral neuropathy [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(8): 13-17.
[5] XIE Haibin, WU Qunzheng, LIU Shaozhuang, HUANG Xin, CHENG Yugang, HU Sanyuan, ZHANG Guangyong. Role of mitochondria-associated membranes in the improvement of insulin sensitivity in diabetic rats after sleeve gastrectomy [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(10): 36-40.
[6] JIANG Yunshan, TAN Hong, LI Xiaoyan, SU Li, ZHANG Guoming, ZHANG Hongming, MENG Nan. Effects of perindopril on the expression of plasma miR-423-5p and cardiac function in patients with heart failure [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(8): 55-59.
[7] CHEN Yihui, LIU Xuewei, HOU Xuhao, SUN Qinfeng. Study of mouse alveolar bone defect reparation by dialdehyde bletilla striata glucomanna / hydroxypropyl chitosan / nano-nacre powder composited scaffolds [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(6): 7-11.
[8] LI Hongzhi, LIU Jing, SONG Yan, CHI Lingyi, LIU Yuguang. Role of liraglutide in the repair of spinal cord injury [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(4): 1-5.
[9] DONG Xiaojing, LI Jing, ZHAO Lei, QI Mei, SUN Zeyu, WANG Hong, ZHAO Weiming. Effect of natural killer cells on the production of interleukin-22 and disease process during Chlamydia muridarum lung infection [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(11): 19-23.
[10] REN Baoxin, MA Yunfeng, LIU Dianwei, LI Zhuo, JIANG Yong. Effects of Wnt3a on neuronal autophagy and apoptosis in early brain injury after subarachnoid hemorrhage in rats [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(10): 11-15.
[11] MAN Qi, ZHANG An, ZHANG Yuan, FAN Mingde, MA Daoxin, WANG Chengwei. Expressions and significance of Th17 and Th22 cells in peripheral blood of patients with glioma [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(10): 55-59.
[12] CHEN Zhixin, WANG Ying, CAO Xinran, HEI Naihao, LI Junlong, DONG Bo, GUAN Guangju. Evaluation of the protective effect of AVE0991 on streptozotocin-induced diabetic nephropathy rats [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(10): 29-33.
[13] ZHANG Dongqing, WANG Yong, CHEN Shouzhen, ZHU Yaofeng, SHI Benkang. Changes on the expressions of alpha1-adrenergic receptor and nerve growth factor and their effects on urethral function in diabetic rats [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(9): 30-34.
[14] TIAN Xinli, JIAO Jun, ZHANG Teng, MA Daoxin, CUI Baoxia. Expression and significance of Th22 and Th17 cells in the peripheral blood of cervical cancer [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(7): 43-47.
[15] FENG Xiaoyu, ZHANG Hongmei, CHE Xuanqiang, KANG Donghong. Therapeutic effects of human osteoblast-stimulating factor on osteoporosis of ovariectomized rats [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(7): 8-12.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!