| SOCS3过表达对实验性自身免疫性心肌炎大鼠CD4+T细胞失衡的影响 |
| 投稿时间：2025-01-08 修订日期：2025-01-14 点此下载全文 |
| 引用本文：张旭,祝峰,吴令琴,金剑,张俞丰,王华,朱佳聪,吕彬王.SOCS3过表达对实验性自身免疫性心肌炎大鼠CD4+T细胞失衡的影响[J].医学研究杂志,2025,54(6):114-120 |
| DOI：
10.11969/j.issn.1673-548X.2025.06.021 |
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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CD4+T细胞失衡的影响及机制。方法 从30只雄性Lewis大鼠中随机选取10只作为对照组,其余20只大鼠在实验第0天和第7天注射猪心肌肌球蛋白,建立EAM大鼠模型。将20只大鼠随机分为EAM组和EAM+SOCS3组。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天对所有大鼠进行超声心动图检查,评估其心脏功能后实施安乐死。采用酶联免疫吸附试验(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型利钠肽和血清细胞因子水平。采用苏木精-伊红(hematoxylin-eosin,HE)染色法评估心肌组织炎症浸润和心肌病理积分,流式细胞仪检测大鼠脾脏中CD4+T细胞亚群水平。采用实时荧光定量聚合酶链反应(real time fluorescent quantitative polymerase chain reaction,RT-qPCR)法和蛋白质印迹(Western blot,WB)法检测SOCS3、Janus激酶2(Janus kinase 2,JAK2)、信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)和CD4+T细胞特异性转录因子的表达。结果 EAM组血清心肌肌钙蛋白T、肌酸激酶同工酶、B型利钠肽的表达水平较对照组上升(P<0.05),心肌病理积分较对照组上升(P<0.05)；EAM组心肌组织中T细胞转录因子(T-box expressed in T cells,T-bet)、维甲酸相关孤核受体γt(retinoid-related orphan receptor γt,RORγt)mRNA和蛋白表达水平较对照组上升(P<0.05),叉状头转录因子P3(forkhead box P3,Foxp3)表达水平下降(P<0.05)；EAM组脾脏中辅助性T细胞1(helper T cell 1,Th1)、辅助性T细胞17(helper T cell 17,Th17)百分比较对照组上升(P<0.05),调节性T细胞(regulatory T cell,Treg)百分比下降(P<0.05)；EAM组心肌组织中JAK2、STAT3mRNA和蛋白的表达水平较对照组上升(P<0.05)。EAM+SOCS3组这些指标较EAM均有不同程度的恢复(P<0.05)。结论 SOCS3过表达可改善EAM大鼠CD4+T细胞失衡,减轻心肌损害,其机制可能与下调JAK2/STAT3信号通路有关。 |
| 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 酪氨酸激酶2/信号转导和转录激活因子 3 通路 CD4+T细胞 |
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| Effect of SOCS3 Overexpression on CD4+ T cells Imbalance in Rats with Experimental Autoimmune Myocarditis. |
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| Abstract:Objective To investigate the effects and mechanisms of suppressor of cytokine signaling 3 (SOCS3) overexpression on CD4+T cells imbalance in rats with experimental autoimmune myocarditis (EAM). Methods Ten male Lewis rats were randomly selected as the control group from 30male Lewis rats. The remaining 20 rats were injected with porcine cardiac myosin on the 0th and 7th days of the experiment to establish the EAM rat model. These 20 rats were then randomly divided into two groups:the EAM group and the EAM + SOCS3group. The EAM + SOCS3group was injected with SOCS3-overexpressing lentivirus via the tail vein, while the EAM group was injected with an equal volume of empty vector lentivirus. All rats underwent echocardiography to evaluate cardiac function and were then euthanized on the 21st day of the experiment. 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 cytokine levels. Myocardial tissue inflammation infiltration and myocardial pathological scores were evaluated by hematoxylin-eosin (HE) staining. The levels of CD4+ T cell subsets in the rat spleen were detected by flow cytometry. The expressions of SOCS3, Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), and CD4+ T cell-specific transcription factors were detected by real time fluorescent quantitative polymerase chain reaction (RT-qPCR) and Western blot. Results In the EAM group, the levels of serum of cardiac troponin T, creatine kinase-myocardial band, and B-type natriuretic peptide, were significantly increased compared with those in the control group (P<0.05), and the myocardial pathological score was significantly increased (P<0.05); In the EAM group, the mRNA and protein expressions of T-box expressed in T cells (T-bet) and retinoid-related orphan receptor γt (RORγt) in myocardial tissues were significantly increased compared with those in the control group (all P<0.05), while the expression of forkhead box P3 (Foxp3) was significantly decreased (P<0.05); In the EAM group, the percentages of helper T cell 1 (Th1) and helper T cell 17 (Th17) in the spleen were significantly increased compared with those in the control group (both P<0.05), and the percentage of regulatory T cell (Treg) was significantly decreased (P<0.05); In the EAM group, the mRNA and protein expressions of JAK2 and STAT3 in myocardial tissues were significantly increased compared with those in the control group (P<0.05). These indexes in the EAM + SOCS3group were significantly restored compared with those in the EAM group(P<0.05). Conclusion SOCS3 overexpression can ameliorate the imbalance of CD4+ T cells and alleviate myocardial damage in EAM rats, and its mechanism is related to the downregulation of the JAK2/STAT3signaling pathway. |
| keywords:Autoimmune myocarditis Suppressors of cytokine signaling 3 Janus kinase 2/signal transducer and activator of transcription 3signal pathway CD4+T cells |
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