基于 ERK1 / 2 和 p38 MAPK 信号通路探讨温阳化饮方对支气管哮喘寒饮蕴肺证大鼠的作用机制
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1.河南省中医院急诊科,郑州 450002;2.青海省人民医院急救中心,西宁 810007

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R-33

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Wenyanghuayin decoction ameliorates the airway remodeling associated with bronchial asthma and syndrome of cold fluid accumulation in the lungs of rats via the ERK1 / 2 and p38 MAPK signaling pathways
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1.Emergency Department, Henan Hospital of Traditional Chinese Medicine, Zhengzhou 450002, China. 2. Emergency Center, Qinghai People’s Hospital, Xining 810007

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    摘要:

    目的 探讨温阳化饮方对支气管哮喘寒饮蕴肺证大鼠的作用以及对 ERK1 / 2 和 p38 MAPK 信号通路的调节作用。 方法 将 SD 大鼠随机分为正常组、模型组、对照组、实验组(n= 15);先以卵蛋白(OVA)致敏刺激和雾化进行造模形成支气管哮喘模型大鼠,后以冰水喂养给以“饮冷”刺激,冰箱冷冻给以“形寒”刺激进行寒饮蕴肺证造模。实验组和对照组大鼠以剂量为 30 mg / kg 的温阳化饮方和雷帕霉素溶液(以医用生理盐水进行溶解)进行灌胃给药,正常组和模型组以等剂量的医用生理盐水灌胃,连续灌胃 22 d。小微动物肺功能分析仪测定大鼠的肺功能;TUNEL 检测肺组织中的细胞凋亡;ELISA 法检测血清中细胞因子白细胞介素 6( IL-6)和肿瘤坏死因子-α (TNF-α)的含量;Western blot 检测肺组织中 p-ERK1 / 2、p-p38 MAPK、凋亡相关蛋白 Bax、Bcl2 的表达。 结果 与正常组相比,模型组大鼠吸气时的气道阻力(Rinsp)和呼气时的气道阻力(Rexp),血清中 IL-6 和 TNF-α 的含量,细胞 凋亡率,p-ERK1 / 2、p-p38 MAPK、Bax 的表达出现明显升高,肺胸通气时的动态顺应性(Cdyn)、Bcl-2 的表达出现明 显下降(均 P<0. 05),与模型组相比,对照组和实验组大鼠 Rinsp 和 Rexp、血清中 IL-6 和 TNF-α 的含量,细胞凋亡 率,p-ERK1 / 2、p-p38 MAPK、Bax 的表达出现明显下降,Cdyn、Bcl-2 出现明显升高(均 P<0. 05)。 结论 在支气管哮喘寒饮蕴肺证大鼠模型中,温阳化饮方能明显抑制炎性因子的释放,降低肺组织的细胞凋亡,这可能与抑制 ERK1 / 2和 p38MAPK 信号有关。

    Abstract:

    Objective To investigate the mechanism whereby Wenyanghuayin decoction ameliorates airway remodeling in rats with bronchial asthma and syndrome of cold fluid accumulation, focusing on the ERK1 / 2 and p38 MAPK signaling pathways. Methods Sprague Dawley rats were randomly allocated to normal, model, control, and experimental groups (n= 15 each). Ovalbumin sensitization, stimulation, and atomization were used to induce bronchial asthma in the model rats, then iced water feeding was stimulated by “ cold drinking” and freezing in a refrigerator was stimulated by “ form cold” to model the syndrome of cold drink accumulating in the lung. Rats in the experimental and control groups were administered 30 mg / kg Wenyanghuayin decoction or rapamycin in physiological saline by gavage, respectively, and the normal and model groups were administered the same volume of normal saline for 22 consecutive days. A small and micro animal lung function analyzer was used to assess the lung function of the rats. TUNEL staining was used to detect cell apoptosis in lung tissue. ELISA kits were used to measure the serum concentrations of interleukin ( IL-6) and tumor necrosis factor-α (TNF-α). Western blot was used to measure the expression of p-ERK1 / 2, p-p38 MAPK, the apoptosis- related protein Bax, and Bcl2 in lung tissue. Results Compared with the normal group, the airway resistance during inhalation (Rinsp) and expiration (Rexp), the serum concentrations of IL-6 and TNF-α, the rate of apoptosis, and the expression of p-ERK1 / 2, p-p38 MAPK, and Bax were significantly higher, and the dynamic compliance ( Cdyn) and expression of Bcl-2 were significantly lower ( all P<0. 05) in the model group than in the control group. The Rinsp and Rexp, serum IL-6 and TNF-α, apoptosis rate, and expression of p-ERK1 / 2, p-p38 MAPK, and Bax were significantly lower; and the Cdyn and the expression of Bcl-2 were significantly higher than in the control and experimental groups (all P<0. 05). Conclusions In a rat model of airway remodeling during bronchial asthma and syndrome of cold fluid accumulation in the lung, Wenyanghuayin decoction significantly inhibits the release of proinflammatory factors and reduces lung cell apoptosis, which may be mediated via inhibition of ERK1 / 2 and p38 MAPK signaling pathways.

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乔 梁,胡山岗,李荣霞.基于 ERK1 / 2 和 p38 MAPK 信号通路探讨温阳化饮方对支气管哮喘寒饮蕴肺证大鼠的作用机制[J].中国比较医学杂志,2021,31(8):93~100.

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  • 收稿日期:2020-08-20
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  • 在线发布日期: 2021-09-26
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