Effect of baotaiyin on IL-23 /Th17 immune inflammatory axis in mouse model of spontaneous abortion

保胎饮对自然流产小鼠IL-23/Th17免疫炎症轴的影响

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作者:Xingxiu Zhan, Lijuan Jiang, Hongping Niu, Lijuan Yang, Qianqian Wan, Yanping Qian

Conclusions

Baotaiyin inhibits the positive feedback cycle of IL-23/Th17 immune inflammatory axis, which regulates Th17/Treg cell balance, mediates the maternal and fetal immune tolerance, and prevents the recurrent abortion. 目的: 中药治疗反复自然流产的机制尚不清楚,本研究探讨中药保胎饮通过调节白介素(interleukin,IL)-23/辅助性T细胞(helper T cell,Th)17免疫炎症轴治疗反复自然流产的作用机制。方法: 将自然流产小鼠模型随机分成模型组,保胎饮低、中、高剂量组,每组10只。用药14 d后,采用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测血清中IL-17、IL-23、转化生长因子β(transforming growth factor,TGF-β)及IL-10的表达水平;流式细胞术检测小鼠脾淋巴细胞中Th17与调节性T细胞(regulatory T cells,Treg)的比例;RT-PCR检测蜕膜组织中维A酸相关孤儿受体γt(retinoid-related orphan receptor γt,ROR-γt)、叉头样转录因子蛋白3(forkhead box protein3,FOXP3)mRNA表达,并计算胚胎吸收率。结果: 与模型组比较,保胎饮中、高剂量组胚胎吸收率和Th17/Treg细胞比值均明显下降(均P<0.05),血清IL-17和IL-23表达均明显降低(均P<0.05),同时TGF-β和IL-10表达均升高(分别P<0.05和P<0.01);蜕膜组织中RORγt mRNA表达降低而FOXP3 mRNA表达升高(均P<0.01)。结论: 保胎饮通过抑制IL-23/Th17免疫炎症轴的正反馈循环,调控Th17/Treg细胞平衡从而介导母胎免疫耐受,防止复发性流产的发生。.

Methods

Spontaneous abortion model mice were randomly divided into a model group, 3 dose (low, medium, and high) groups of baotaiyin, with 10 mice in each group. After 14 days of medication, the levels of IL-17, IL-23, IL-10, and TGF-β in serum were detected with enzyme-linked immunosorbent assay. The proportion of Th17 and regulatory T cells (Treg) cells in spleen lymphocytes was tested with flow cytometry. The expressions of (retinoid-related orphan receptor γt, ROR-γt) and forkhead box P3 (FOXP3) mRNA in decidua tissues was detected with RT-PCR. Embryo absorption rate was counted.

Results

Compared with the model group, the absorption rate of embryo and Th17/Treg cell ratio in baotaiyin medium- and high-dose groups were decreased significantly (all P<0.05); the levels of IL-17 and IL-23 in serum were decreased (both P<0.05), while the levels of TGF-β and IL-10 in baotaiyin medium- and high-dose groups were increased (P<0.05, P<0.01, respectively); the expression of ROR-γt mRNA was decreased and the expression of FOXP3 mRNA was increased (all P<0.01) in decidua tissues of baotaiyin medium- and high-dose groups. Conclusions: Baotaiyin inhibits the positive feedback cycle of IL-23/Th17 immune inflammatory axis, which regulates Th17/Treg cell balance, mediates the maternal and fetal immune tolerance, and prevents the recurrent abortion. 目的: 中药治疗反复自然流产的机制尚不清楚,本研究探讨中药保胎饮通过调节白介素(interleukin,IL)-23/辅助性T细胞(helper T cell,Th)17免疫炎症轴治疗反复自然流产的作用机制。方法: 将自然流产小鼠模型随机分成模型组,保胎饮低、中、高剂量组,每组10只。用药14 d后,采用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测血清中IL-17、IL-23、转化生长因子β(transforming growth factor,TGF-β)及IL-10的表达水平;流式细胞术检测小鼠脾淋巴细胞中Th17与调节性T细胞(regulatory T cells,Treg)的比例;RT-PCR检测蜕膜组织中维A酸相关孤儿受体γt(retinoid-related orphan receptor γt,ROR-γt)、叉头样转录因子蛋白3(forkhead box protein3,FOXP3)mRNA表达,并计算胚胎吸收率。结果: 与模型组比较,保胎饮中、高剂量组胚胎吸收率和Th17/Treg细胞比值均明显下降(均P<0.05),血清IL-17和IL-23表达均明显降低(均P<0.05),同时TGF-β和IL-10表达均升高(分别P<0.05和P<0.01);蜕膜组织中RORγt mRNA表达降低而FOXP3 mRNA表达升高(均P<0.01)。结论: 保胎饮通过抑制IL-23/Th17免疫炎症轴的正反馈循环,调控Th17/Treg细胞平衡从而介导母胎免疫耐受,防止复发性流产的发生。.

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