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目的通过观察鼻内注射γ-氨基丁酸受体(GABAR)特异性拮抗剂荷包牡丹碱对慢性哮喘模型小鼠肺组织α-平滑肌肌动蛋白(alpha-smooth muscle actin,α-SMA)在转录水平及蛋白水平表达及气道重构的影响,探讨拮抗剂在哮喘气道重构中的治疗作用。方法将BALB/c小鼠随机分为正常对照组、哮喘模型组、拮抗剂干预组和激素干预组,用卵蛋白(OVA)致敏激发建立小鼠哮喘模型,采用逆转录聚合酶链反应(RT-PCR)与免疫组化的方法研究肺组织α-SMA的表达及气道形态学参数的改变。结果①与正常对照组比较,在激发哮喘后哮喘模型组肺组织α-SMA的表达升高(P<0.05);与哮喘模型组相比较,各药物干预组α-SMA的表达均降低(P<0.01);拮抗剂干预组和激素干预组比较,小鼠肺组织α-SMA表达无明显差异(P>0.05);②与正常组比较,哮喘模型组支气管基底膜周径(Pbm)、管壁总面积(WAt)、内壁面积(WAi)及平滑肌面积(WAm)均增高(P<0.05);与哮喘模型组比较,激素干预组气道形态学参数均下降(P<0.01),拮抗剂组气道平滑肌面积和管壁总面积下降(P<0.05),各药物干预组比较无明显差异(P>0.05)。结论哮喘小鼠肺组织α-SMA过量表达与哮喘发生密切相关,荷包牡丹碱可以抑制慢性哮喘模型小鼠α-SMA的表达及气道形态结构改变,作用与吸入性皮质激素相似。提示GABAR通过上调α-SMA表达,促进气道平滑肌收缩及增生,参与气道重构的调节。
Objective To observe the effects of intranasal injection of bicuculline, a GABAR antagonist, on the expression of α-smooth muscle actin (α-SMA) in the lung tissue of chronic asthmatic mice Level and protein expression and airway remodeling, and explore the therapeutic effect of antagonist in airway remodeling of asthma. Methods BALB / c mice were randomly divided into normal control group, asthma model group, antagonist intervention group and hormone intervention group. Asthma model was established by sensitization with ovalbumin (OVA). Reverse transcription polymerase chain reaction RT-PCR) and immunohistochemistry were used to study the expression of α-SMA in lung tissue and the change of airway morphology parameters. Results ① Compared with the normal control group, the expression of α-SMA in asthmatic model group was significantly increased (P <0.05); Compared with the asthma model group, the expression of α-SMA decreased <0.01). There was no significant difference in α-SMA expression in the lung tissue between the intervention group and the hormone intervention group (P> 0.05). ② Compared with the normal group, the bronchial basement membrane (Pbm) The total wall area (WAt), inner wall area (WAi) and smooth muscle area (WAm) of the asthma model group were significantly higher than those of the asthma model group (P <0.01) The airway smooth muscle area and the total area of the wall decreased (P <0.05). There was no significant difference between each drug intervention group (P> 0.05). Conclusion The overexpression of α-SMA in lung tissue of asthmatic mice is closely related to the development of asthma. Bicuculline can inhibit the expression of α-SMA and the change of airway morphology in mice with chronic asthma, which is similar to that of inhaled corticosteroids. These results suggest that GABAR may be involved in the regulation of airway remodeling by up-regulating the expression of α-SMA and promoting airway smooth muscle contraction and proliferation.