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心衰过程中β3 AR自身抗体的产生与T细胞亚群变化的相关研究
Dynamic changes of T cell subsets in peripheral blood and their relationships with the emergence of autoantibody against beta3-adrenoceptor in rats during development of heart failure
【摘要】 目的:分析心力衰竭大鼠外周血T细胞亚群变化与β3AR自身抗体产生的规律,并探讨其相关意义。方法:采用腹主动脉缩窄法制备大鼠心力衰竭模型,并设立伪手术对照组;定期采用ELISA技术检测大鼠血清中β3AR自身抗体含量,并应用流式细胞术检测大鼠外周血CD4+、CD8+T细胞、CD4+CD25+Treg及CD4+CD25+Foxp3+Treg细胞的比例。结果:(1)心衰组大鼠在腹主动脉缩窄术处理后8周心功能明显下降,出现心肌重塑,心衰模型成功建立。(2)心衰组大鼠血清中β3AR自身抗体水平(OD值)在术后4周即升高,与同期伪手术对照组具有明显差异(P<0.05);该抗体在术后8周时达峰值,与同期伪手术对照组具有显著差异(P<0.01);至12周时,β3AR自身抗体水平有所下降但与同期伪手术对照组仍具有明显差异(P<0.05);术后16周时,该抗体水平与同期伪手术对照组无明显差异(P>0.05)。(3)腹主动脉缩窄术处理4周、8周时,心衰组大鼠外周血CD4+T细胞比例及CD4+/CD8+T比值升高,CD4+CD25+Treg/CD4+T及CD4+CD25+Foxp3+Treg/CD4+T比例降低,与同期伪手术对照组的差异均具有统计学意义(P<0.05);处理12周、16周时,心衰组大鼠外周血CD4+T细胞比例、CD4+/CD8+T比值、CD4+CD25+Treg/CD4+T及CD4+CD25+Foxp3+Treg/CD4+T比例与同期伪手术对照组无明显差异(P>0.05)。(4)β3AR自身抗体水平与CD4+T细胞含量呈正相关,与CD4+CD25+Treg及CD4+CD25+Foxp3+Treg细胞含量呈负相关。结论:在心衰发病过程中产生了β3AR自身抗体并伴有明显的T细胞亚群失衡,CD4+CD25+Foxp3+Treg细胞可能对调控β3AR自身抗体的产生起重要作用。
【Abstract】 Objective:To investigate the change of CD4+and CD4+CD25+regulatory T cells(Treg) in peripheral blood in rats with heart failure(HF) and its significance of the emergence of autoantibody against beta3-adrenoceptor(β 3 AR).Methods:Heart failure in rat was induced by constricted the abdominal aorta.The percentages of CD4+,CD8+,CD4+CD25+and CD4+CD25+Foxp3+T lymphocyte in the peripheral blood were detected by flow cytometry and autoantibody against β 3 AR was detected by ELISA.Results:(1) The heart failure model was successively constructed as evidenced by morphological examination results and impaired cardiac function at 8 weeks after abdominal aorta banding.(2) In HF group,autoantibodies to β 3 AR in the sera was increased at 4 weeks after treatment and considerably increased at 8 weeks after treatment and appeared to keep until 12 weeks after treatment as compared with sham group.However,it was no significance between HF and sham group at 16 weeks after treatment.(3) In HF group,the percentage of CD4+in peripheral blood was considerably increased at 4 and 8 weeks after treatment(P<0.05),in the mean time,the percentage of CD4+CD25+and CD4+CD25+Foxp3+Treg in peripheral blood was considerably decreased as compared with sham group(P<0.05).Then,the percentage of CD4+and CD4+CD25+and CD4+CD25+Foxp3+Treg in the peripheral blood were no significant differences between HF and sham groups(P>0.05).(4) Anti-β 3 AR antibody level was positively correlated with CD4+T cells and negative correlated with CD4+CD25+Treg and CD4+CD25+Foxp3+Treg cells.Conclusion:There appears high value of β 3 AR autoantibodies and obvious unbalance of T cell subsets in the pathogenesis of heart failure,and CD4+CD25+Foxp3+Treg cells may play an important role on the regulation of anti-β 3 AR antibodies.
【Key words】 Heart failure; Autoantibody,beta3-adrenoceptor; T lymphocyte,subsets; T lymphocyte,regulatory;
- 【文献出处】 中国免疫学杂志 ,Chinese Journal of Immunology , 编辑部邮箱 ,2013年09期
- 【分类号】R541.6
- 【被引频次】5
- 【下载频次】121