白头翁皂苷B4基于调节巨噬细胞极化对小鼠溃疡性结肠炎的影响

doi:10.20047/j.issn1673-7210.2023.07.05

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摘要目的探究白头翁皂苷B4基于调节巨噬细胞极化对葡聚糖硫酸钠（DSS）诱导的溃疡性结肠炎（UC）小鼠的作用。方法将40只SPF级雄性C57BL/6小鼠（体重18～20 g）按随机数字表法分为对照组、模型组、B4组和阳性药组，每组10只。模型组、B4组和阳性药组连续给予3%DSS 5 d构建UC模型，造模成功后B4组灌胃白头翁皂苷B4（5 mg/kg，1次/d），阳性药组灌胃美沙拉秦（400 mg/kg，1次/d），对照组和模型组灌胃等量生理盐水，四组均连续干预7 d。观察干预期间小鼠体重的变化。干预结束后对小鼠结肠组织进行苏木精-伊红染色并进一步评估其病理组织学指数，并对四组炎症相关指标进行检测。qRT-PCR检测四组结肠组织中核因子κB（NF-κB）p50、p65及M1型巨噬细胞特异性指标诱生型一氧化氮合酶（iNOS）、M2型巨噬细胞特异性指标精氨酸-1（Arg1）的mRNA表达水平。对四组结肠组织进行免疫组织化学染色，观察四组结肠组织中巨噬细胞极化的情况。结果模型组干预6、9、12 d的体重均低于对照组，B4组干预12 d的体重高于模型组（P＜0.05或P＜0.01）。对照组黏膜层肠腺排列整齐，无溃疡性病变；模型组肠黏膜层隐窝及上皮大部分丧失，并伴有大量炎症细胞浸润、炎症侵及黏膜层和黏膜下层；B4组结肠黏膜具有轻微炎症，溃疡和出血症状明显减少，上皮和隐窝较为完整，结肠黏膜损伤也得到显著改善。模型组病理组织学指数、肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-6水平及核因子κB（NF-κB）p50、NF-κBp65、iNOS mRNA表达水平高于对照组，IL-10、转化生长因子-β（TGF-β）水平及Arg1 mRNA表达水平低于对照组（P＜0.05）。B4组病理组织学指数、TNF-α、IL-1β、IL-6水平及NF-κBp50、NF-κBp65、iNOS mRNA表达水平低于模型组，IL-10、TGF-β水平及Arg1 mRNA表达水平高于模型组（P＜0.05）。模型组M1型巨噬细胞比例高于对照组，M2型巨噬细胞比例低于对照组，B4组M1型巨噬细胞比例低于模型组，M2型巨噬细胞比例高于模型组（P＜0.05）。结论白头翁皂苷B4可通过抑制M1型巨噬细胞极化，促进M2型巨噬细胞极化，改善肠道炎症环境，缓解UC。

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	孙洁1 史肖华1 李彩云2 季士亮2

关键词 ：白头翁皂苷B4, 溃疡性结肠炎, 巨噬细胞, 极化

Abstract：Objective To investigate the effect of Anemoside B4 on ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in mice based on regulation of macrophage polarization. Methods Forty SPF male C57BL/6 mice (body weight 18-20 g) were divided into control group, model group, B4 group, and positive drug group by random number table method, with ten mice in each group. Model group, B4 group, and positive drug group were given 3%DSS for five days consecutively to construct UC model. After successful modeling, B4 group was given intragastric administration of Anemoside B4 (5 mg/kg, once a day), positive drug group was given intragastric administration of Mesalazine (400 mg/kg, once a day), control group and model group were given intragastric administration of the same amount of normal saline. All four groups were given continuous intervention for seven days. The changes of mice body weight during the intervention were observed. After the intervention, the colon tissues of mice were stained with hematoxylin-eosin, and the histopathological index was further evaluated, and the inflammatory indicators of four groups were detected. The mRNA expression levels of nuclear factor-κB (NF-κB) p50, p65, and M1 macrophages type specific index inducible nitric oxide synthase (iNOS), M2 macrophages type specific index arginine-1 (Arg1) in colon tissues of the four groups were detected by qRT-PCR. The polarization of macrophages in the colon tissues of the four groups was observed by immunohistochemical staining. Results The body weight of the model group was lower than those of the control group at 6, 9, and 12 d after intervention, while the body weight of the B4 group at 12 d after intervention was higher than that of the model group (P＜0.01 or P＜0.05). In the control group, mucosal intestinal glands were arranged neatly without ulcerative lesions. In the model group, most of the crypts and epithelium of the intestinal mucosal layer were lost, accompanied by a large number of inflammatory cell infiltration, inflammatory invasion of the mucosal layer and submucosa. In B4 group, the colonic mucosa had slight inflammation, ulcer, and bleeding symptoms were significantly reduced, the epithelium and recess were relatively intact, and the colonic mucosa injury was also significantly improved. Histopathological index, levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and mRNA expression levels of NF-κB p50, NF-κBp65, iNOS in model group were higher than those in control group, levels of IL-10, transforming growth factor-β (TGF-β), and mRNA expression level of arginine-1 (Arg1) were lower than those in control group (P＜0.05). Histopathological index, levels of TNF-α, IL-1β, IL-6, and mRNA expression levels of NF-κBp50, NF-κBp65, iNOS in B4 group were lower than those in model group, levels of IL-10, TGF-β, and mRNA expression level of Arg1 were higher than those in model group (P＜0.05). The proportion of M1 macrophages in the model group was higher than that in the control group, and the proportion of M2 macrophages was lower than that in the control group, the proportion of M1 macrophages in the B4 group was higher than that in the model group, and the proportion of M2 macrophages was higher than that in the model group (P＜0.05). Conclusion Anemoside B4 can inhibit the M1 macrophages, promote the M1 macrophages, improve the intestinal inflammatory environment and relieve UC.

Key words： Anemoside B4 Ulcerative colitis Macrophages Polarization

基金资助:江苏省中医药局科技项目（YB2020064）；
江苏省苏州市高新区医疗卫生人才项目；
江苏省苏州市科教兴卫青年科技项目（KJXW2020082）。

通讯作者: 季士亮（1990.2-），男，南京大学生命科学学院2021级生物医药专业在读博士研究生；研究方向：中药药理。

作者简介: 孙洁（1988.4-），女，硕士；研究方向：炎症性肠病。

引用本文:

孙洁1 史肖华1 李彩云2 季士亮2. 白头翁皂苷B4基于调节巨噬细胞极化对小鼠溃疡性结肠炎的影响[J]. 中国医药导报, 2023, 20(7): 27-31.
SUN Jie1 SHI Xiaohua1 LI Caiyun2 JI Shiliang2. Influence of Anemoside B4 on ulcerative colitis in mice based on regulation of macrophage polarization. 中国医药导报, 2023, 20(7): 27-31.

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https://www.yiyaodaobao.com.cn/CN/10.20047/j.issn1673-7210.2023.07.05 或 https://www.yiyaodaobao.com.cn/CN/Y2023/V20/I7/27

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