南方医科大学学报

南方医科大学学报 ›› 2021, Vol. 41 ›› Issue (2): 256-263.doi: 10.12122/j.issn.1673-4254.2021.02.14

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黄芩汤通过调节ILC3s-Th细胞反应减轻小鼠的溃疡性结肠炎

周长琳, 郑学宝, 黄晓其, 苏冀彦, 李木霞, 陈志维, 李敏瑶, 迟宏罡   

  • 发布日期:2021-02-05

Huangqin decoction alleviates ulcerative colitis by regulating ILC3s-TH cell response

  • Published:2021-02-05

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摘要：

目的 探讨黄芩汤在治疗溃疡性结肠炎（UC）过程中对三型固有淋巴细胞（ILC3）及辅助性T细胞（Th）免疫反应的调控作用。方法 将雄性Balb/c小鼠随机分为6组：正常组、模型组、美沙拉嗪组、黄芩汤低、中、高剂量组（HL，2.275 g/kg；HM，4.55 g/kg；HH，9.1 g/kg）。各组自由饮食，除正常组自由饮用蒸馏水外，其余各组小鼠自由饮用3%葡聚糖硫酸钠溶液，持续7d以建立UC模型，同时美沙拉嗪组和黄芩汤低、中、高剂量组小鼠每日分别给予美沙拉嗪及低、中、高剂量黄芩汤灌胃1次。流式细胞术分析结肠固有层淋巴细胞中ILC3s细胞比例及其表面主要组织相容性复合物Ⅱ类（MHCⅡ）分子表达变化以及Th细胞中Th1与调节性T细胞（Treg）的比例变化。采用Milliplex 多因子测定方法检测结肠组织中多个细胞因子含量的变化。结果 与模型组相比，黄芩汤各剂量组小鼠溃疡性结肠炎症状得以缓解，疾病活动指数评分及宏观评分下降（P<0.001）。流式细胞术结果表明，黄芩汤各剂量组小鼠结肠中ILC3s细胞比例增加（P<0.05）且MHCⅡ分子表达增多（P<0.05），其中黄芩汤低、中剂量组Th1细胞比例降低（P<0.05）而Treg细胞比例增加（P<0.05）。Milliplex 多因子测定结果表明，黄芩汤各剂量组小鼠结肠组织中Th细胞相关的促炎性细胞因子如白介素-2、白介素-17A、白介素-23、α肿瘤坏死因子、γ干扰素含量降低（P<0.05）。结论 黄芩汤通过增加ILC3s细胞数目及其MHCⅡ的表达，调节Th细胞免疫反应，从而缓解DSS诱导的小鼠溃疡性结肠炎。

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Abstract:

Objective To explore the effect of Huangqin decoction (HQD) on group 3 innate lymphoid cells (ILC3s) and helper T
cells (Th) for treatment of ulcerative colitis (UC). Methods Male Balb/c mice were randomly divided into control group, DSS group, mesalazine group (ME, 400 mg/kg), and 2.275 g/kg, 4.55 g/kg and 9.1 g/kg HQD groups. All the mice were given free access to normal chow. Except for those in the normal control group, all the mice were given 3% DSS solution for 7 days to establish models of UC. The mice in ME group and 3 HQD groups were given mesalazine or HQD via oral gavage at the specified doses once a day. Flow cytometry was performed to analyze the ILC3s, MHC II, Th1 and Treg in the lamina propria lymphocytes in the colon. Milliplex was performed to determine cytokine levels of in the colon tissues. Results Compared with those in DSS group, the mice in the 3 HQD groups all showed obviously lessened symptoms of UC with significantl decreased DAI score (P<0.001) and macroscopic score (P<0.001). The results of flow cytometry showed that HQD treatment significantly increased the percentage of ILC3s (P<0.05) and expression of MHCⅡ (P<0.05), obviously reduced the proportion of Th1 (P<0.05) but increased Treg cells (P<0.05) in the colon tissues. Milliplex showed that HQD treatment significantly reduced the expressions of Th-related pro-inflammatory cytokines including IL-2 (P<0.05), IL-17A (P<0.05), IL-23 (P<0.05), TNF-α (P<0.05), and IFN- γ (P<0.05). Conclusion HQD alleviates DSS- induced UC in mice by increasing ILC3s and MHC Ⅱ expression to suppress the function of Th17 and Th1 cells and promote Treg and Th2 cells.

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