二甲双胍灌胃对支气管哮喘小鼠气道重塑的影响及机制探讨

发布时间：2018-06-02 08:35

本文选题：哮喘 + 二甲双胍　；参考：《山东医药》2017年47期

【摘要】：目的观察二甲双胍灌胃对支气管哮喘小鼠气道重塑的影响,并探讨其可能机制。方法将30只清洁级C57BL/6雌性小鼠随机分为对照组、模型组、观察组各10只。模型组及观察组于实验第0、7、14天腹腔注射100μg卵清蛋白(OVA)+2 mg氢氧化铝致敏,并在第21~60 d采用50μg OVA(3次/周)滴鼻激发建立支气管哮喘模型;对照组以等量生理盐水腹腔注射致敏及滴鼻激发。自第21天起,观察组小鼠灌胃300 mg/(kg·d),模型组及对照组灌胃等量生理盐水。行HE染色观察肺组织病理情况,masson染色下利用Image-Pro Plus 6.0图像分析系统测算气道基底膜下胶原面积比及支气管壁、平滑肌厚度,ELISA法检测血清转化生长因子β1(TGF-β1)、基质金属蛋白酶9(MMP-9)、基质金属蛋白酶抑制剂1(TIMP-1),RT-PCR法检测肺组织MMP-9、TIMP-1 mRNA。结果对照组支气管、肺泡等结构相对完整;模型组小鼠见支气管管壁增厚,气道黏膜上皮增生,气管内黏液渗出,肺泡结构破坏等明显;观察组上述改变较模型组明显减轻。与对照组比较,模型组及观察组气道基底膜下胶原面积比、支气管壁厚度、平滑肌细胞厚度增加,血清TGF-β1、MMP-9、TIMP-1水平及肺组织MMP-9、TIMP-1 mRNA表达升高(P均0.05);与模型组比较,观察组气道基底膜下胶原面积比、支气管壁厚度、平滑肌细胞厚度减少,血清TGF-β1、MMP-9、TIMP-1水平及肺组织MMP-9、TIMP-1 mRNA表达降低(P均0.05)。结论二甲双胍可改善支气管哮喘气道重塑,其机制可能为抑制TGF-β1、MMP-9、TIMP-1表达。
[Abstract]:Objective to observe the effect of metformin on airway remodeling in asthmatic mice and explore its possible mechanism. Methods Thirty clean grade C57BL/6 female mice were randomly divided into control group (n = 10), model group (n = 10) and observation group (n = 10). The model group and the observation group were sensitized with 100g ovalbumin (OVA) 2 mg by intraperitoneal injection on day 714 of the experiment, and the asthmatic model was established by nasal drip of 50 渭 g OVA(3 per week on the 21st day of the 60th day. The control group was sensitized by intraperitoneal injection of the same amount of normal saline and stimulated by nasal drip. From the 21st day, the mice in the observation group were given intragastric administration of 300 mg/(kg dU, and the model group and the control group were given the same amount of normal saline. The pathological changes of lung tissue were observed by HE staining. The area ratio of collagen in subbasement membrane of airway and the bronchial wall were measured by Image-Pro Plus 6.0 image analysis system under masson staining. The levels of serum TGF- 尾 1, matrix metalloproteinase 9 (MMP-9), matrix metalloproteinase inhibitor 1 (TIMP 1) and TIMP-1 mRNA in lung tissue were detected by smooth muscle thickness Elisa (Elisa). Results the bronchial and alveolar structures in the control group were relatively intact, the bronchial wall thickened, the airway mucous epithelium proliferated, the mucus exudate in the trachea and the alveolar structure destroyed in the model group, and the above changes in the observation group were significantly less than those in the model group. Compared with the control group, the area ratio of airway basement membrane collagen, the thickness of bronchial wall, the thickness of smooth muscle cells, the level of serum TGF- 尾 1, MMP-9 and TIMP-1 and the expression of MMP-9 and TIMP-1 mRNA in lung tissue were all increased in model group and observation group (P < 0.05). In the observation group, the area ratio of collagen, the thickness of bronchial wall, the thickness of smooth muscle cells, the level of TIMP-1 in serum TGF- 尾 1 and the expression of TIMP-1 in lung tissue were all decreased (P < 0.05). Conclusion Metformin can improve airway remodeling in bronchial asthma by inhibiting the expression of TGF- 尾 1 and MMP-9 and TIMP-1.
【作者单位】：西南医科大学附属医院;
【分类号】：R562.25

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