| 慢病毒介导SOCS3过表达通过下调MCP-1、TGF-β减轻实验性自身免疫性心肌炎 |
| 投稿时间：2024-11-22 修订日期：2024-12-01 点此下载全文 |
| 引用本文：张海东,金剑,张俞丰,王华,朱佳聪,祝峰,吴令琴.慢病毒介导SOCS3过表达通过下调MCP-1、TGF-β减轻实验性自身免疫性心肌炎[J].医学研究杂志,2025,54(5):110-117 |
| DOI：
10.11969/j.issn.1673-548X.2025.05.021 |
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| 基金项目:浙江省医药卫生科技计划项目(2023KY1215) |
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| 中文摘要:目的 探讨慢病毒介导细胞因子信号转导抑制因子3(suppressors of cytokine signaling 3,SOCS3)过表达对实验性自身免疫性心肌炎(experimental autoimmune myocarditis,EAM)大鼠心脏的作用及其机制。方法 30只Lewis大鼠随机分为对照组、EAM组和EAM+SOCS3组。通过皮下注射在心肌肌球蛋白构建EAM大鼠模型。实验第0天EAM+SOCS3组尾静脉注射过表达SOCS3慢病毒,EAM组尾静脉注射等量空载体慢病毒。实验第21天所有大鼠进行超声心动图评估心脏功能并实施安乐死。苏木精-伊红(Hematoxylin-eosin,HE)染色法观察心肌组织病理学变化。酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)法检测血清心肌肌钙蛋白T、肌酸激酶同工酶、B型利钠肽和心肌白细胞介素-6、白细胞介素-1β、肿瘤坏死因子-α。免疫组织化学法、实时荧光定量PCR(realtime quantitative PCR,RT-qPCR)法和Western blot法检测心肌组织SOCS3、Janus激酶2(tyrosine kinase 2,JAK2)、信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)、单细胞趋化因子蛋白1(monocyte chemoattractant protein-1,MCP-1)和转化生长因子-β(transforming growth factor-β,TGF-β)的表达。结果 EAM组心肌病理积分、血清心肌肌钙蛋白T、肌酸激酶同工酶、B型利钠肽水平和心肌白细胞介素-6、白细胞介素-1β、肿瘤坏死因子-α水平明显高于对照组(P<0.05),EAM组的心功能明显低于对照组(P<0.05),EAM组心肌JAK2、STAT3、MCP-1、TGF-β mRNA和蛋白表达明显高于对照组(P<0.05), EAM+SOCS3组这些指标较EAM均有不同程度的恢复(P<0.05)。EAM+SOCS3组心肌中SOCS3mRNA和蛋白表达显著高于EAM组(P<0.05)。结论 SOCS3过表达可能是通过抑制JAK2/STAT3信号通路,下调MCP-1、TGF-β的表达,减轻EAM大鼠心肌的炎性反应,并提高了心脏功能。 |
| 中文关键词:自身免疫性心肌炎 细胞因子信号转导抑制因子3 Janus激酶2/信号转导和转录激活因子3通路 单细胞趋化因子蛋白1 转化生长因子-β |
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| Lentivirus-mediated SOCS3 Overexpression Ameliorates Experimental Autoimmune Myocarditis by Downregulating MCP-1 and TGF-β . |
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| Abstract:Objective To investigate the effect and mechanism of lentivirus-mediated overexpression of suppressors of cytokine signaling 3 (SOCS3) on the heart of rats with experimental autoimmune myocarditis (EAM). Methods Thirty Lewis rats were randomly divided into a control group, EAM group and EAM+SOCS3 group. The EAM rat model was established by subcutaneous injection of cardiac myosin. On day 0 of the experiment, the EAM+SOCS3 group was injected with lentivirus overexpressing SOCS3 via the tail vein, and the EAM group was injected with an equal amount of empty vector lentivirus. On day 21 of the experiment, all rats underwent echocardiography to evaluate cardiac function and were then euthanized. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of myocardial tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum cardiac troponin T, creatine kinase - myocardial band, B-type natriuretic peptide, and myocardial interleukin-6, interleukin-1β and tumor necrosis factor-α. Immunohistochemistry, real-time quantitative PCR (RT-qPCR) and Western blot (WB) were used to detect the expressions of SOCS3, Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-β (TGF-β) in myocardial tissue. Results The myocardial pathological score, serum levels of cardiac troponin T, creatine kinase - myocardial band, B-type natriuretic peptide, and myocardial levels of interleukin-6, interleukin-1β, and tumor necrosis factor - α in the EAM group were significantly higher than those in the control group(P<0.05). The cardiac function of the EAM group was significantly lower than that of the control group(P<0.05). The mRNA and protein expressions of myocardial JAK2, STAT3, MCP-1 and TGF-β in the EAM group were significantly higher than those in the control group(P<0.05). These indexes in the EAM+SOCS3 group were significantly restored compared with those in the EAM group(P<0.05).The mRNA and protein expressions of SOCS3 in the myocardial tissue of the EAM+SOCS3 group were significantly higher than those in the EAM group(P<0.05).Conclusion Overexpression of SOCS3 may ameliorates the inflammatory response of the myocardium in EAM rats and improve cardiac function by inhibiting the JAK2/STAT3 signaling pathway and downregulating the expressions of MCP-1 and TGF-β. |
| keywords:Autoimmune myocarditis Suppressors of cytokine signaling 3 Janus kinase 2/signal transducer and activator of transcription 3 pathway Monocyte chemoattractant protein-1 Transforming growth factor-β |
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