和厚朴酚通过 Not 小 ch 信号通路抑制慢性阻塞性肺疾病鼠免疫失衡并提供肺保护作用
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河南省中医院肺病科,郑州 450002

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R-33

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Honokiol inhibits immune imbalance and provides lung protection in mice with chronic obstructive pulmonary disease through the Notch signaling pathway
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Henan Province Hospital of Traditional Chinese Medicine, Department of Pulmonary Disease, Zhengzhou 450002, China

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    摘要:

    目的 探讨和厚朴酚(HNK)对慢性阻塞性肺疾病(COPD)小鼠免疫失衡及肺功能的影响,并考察 Notch 信号通路是否介导该过程。 方法 将 30 只 6 ~ 8 周龄雄性 BALB/ c 小鼠随机分为 3 组:正常对照组 (Normal)、COPD 组和 COPD+HNK 组,每组 10 只。 通过香烟烟雾诱导 COPD 小鼠模型,然后对 COPD+HNK 组小鼠隔日腹腔注射 HNK(10. 00 mg / kg),共 30 d。 采用法国 EMKA GYD-003 型动物肺功能测试系统检测吸气峰流速 (PIF)和呼气峰流速(PEF)。 苏木精-伊红(HE) 染色评价肺组织病理变化。 用流式细胞仪检测小鼠脾 T 细胞 Th1 / Th2 和 Th17 / Treg 亚群的比值。 Western blot 检测 T 细胞中 Notch 1 / 2 / 3 / 4、Hes1、Hes5 和 Hey1 的蛋白表达。 采用 ELISA 法检测小鼠血清 IFN-γ、IL-4、IL-17 和 IL-10 水平。 结果 与 COPD 组相比,COPD+HNK 组小鼠的 PIF 和 PEF 均显著升高(P<0. 05)。 COPD+HNK 组小鼠肺组织病变较 COPD 组减轻,炎性细胞浸润减少,肺泡数增多,肺泡腔缩小。 与 COPD 组相比,COPD+HNK 组小鼠的 Th1 百分比、Th1 / Th2 比值、Th17 百分比和 Th17 / Treg 比值均显 著降低(P<0. 05)。 与 COPD 组相比,COPD+HNK 组小鼠脾 T 细胞中的 Notch1、Notch2、Notch3、Notch4、Hes1、Hes5、 Hey1 的蛋白相对表达量均显著降低(P<0. 05)。 与 COPD 组相比,COPD+HNK 组小鼠血清中的 IFN-γ 和 IL-17 水平均显著降低(P<0. 05),而 IL-4 和 IL-10 水平显著升高(P<0. 05)。 结论 和厚朴酚通过抑制 COPD 小鼠脾 T 细胞 Notch 信号通路的激活,进而纠正了 COPD 小鼠 Th1 / Th2 和 Th17 / Treg 细胞的失衡,从而改善了肺功能。

    Abstract:

    Objective To investigate the effect of honokiol (HNK) on immune imbalance and lung function in chronic obstructive pulmonary disease (COPD) mice and to investigate whether the Notch signaling pathway mediates this process. Methods BALB/ c mice (male, 6~ 8 weeks old) were randomly divided into three groups: normal control group (Normal), COPD group and COPD+HNK group ( n= 10 mice per group). A mouse model of COPD was induced by cigarette smoke, and HNK (10 mg / kg) was intraperitoneally injected into the COPD+HNK group every other day for 30 days. The French EMKA GYD-003 animal lung function test system was used to detect the peak inspiratory flow rate (PIF) and peak expiratory flow rate (PEF). Hematoxylin-eosin (HE) staining was used to evaluate the pathological changes of lung tissue. Flow cytometry was used to detect the ratio of Th1 / Th2 and Th17 / Treg subgroups of mouse spleen T cells. Western blot was used to examine the protein expression of Notch 1 / 2 / 3 / 4, Hes1, Hes5 and Hey1 in T cells. ELISA was used to detect the levels of serum IFN-γ, IL-4, IL-17 and IL-10 in mice. Results The PIF and PEF of the COPD+HNK group mice were significantly increased compared with result in the COPD group (P<0. 05). In addition, the lung tissue lesions of the mice in the COPD+HNK group were reduced, the inflammatory cell infiltration was reduced, the number of alveoli increased and the alveolar cavity was reduced compared with result in the COPD group. Compared with the COPD group, the COPD+HNK group mice showed significantly reduced Th1 percentage, Th1 / Th2 ratio, Th17 percentage and Th17 / Treg ratio (P<0. 05). In addition, the relative expression levels of Notch1, Notch2, Notch3, Notch4, Hes1, Hes5 and Hey1 in the spleen T cells of the COPD+HNK group mice were significantly reduced (P<0. 05). The levels of IFN-γ and IL-17 in the serum of the COPD+HNK group were significantly reduced (P<0. 05), while the levels of IL-4 and IL-10 were significantly increased (P<0. 05). Conclusions HNK inhibits activation of the Notch signaling pathway of T cells in the spleen of COPD mice, thereby correcting the imbalance of Th1 / Th2 and Th17 / Treg cells in COPD mice and improving lung function.

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李 彬,甘德堃,王璐璐.和厚朴酚通过 Not 小 ch 信号通路抑制慢性阻塞性肺疾病鼠免疫失衡并提供肺保护作用[J].中国比较医学杂志,2022,32(4):86~93.

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  • 收稿日期:2021-07-14
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  • 在线发布日期: 2022-06-20
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