Ren Xu-Bin, Liu Chun-Tao, Zhu Tao
Department of Respiratory Medicine, Division of Pulmonary Diseases, West China Hospital, Sichuan University, Chengdu 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2010 Jul;41(4):626-9.
To observe the effect of bicuculline, which is a selective GABA receptor antagonist on expression of alpha-SMA in the lung tissue of rats with chronic asthma, to explore the role of the bicuculline on the airway remodeling in asthmatic mice.
Forty BALB/c mice were randomly divided into four groups: the control group (A), the asthma model group (B), the bicuculline group (C) and bicuculline with budesonide group (D). The asthmatic model was established by sensitization and challenge with ovalbumin. The expression of alpha-SMA in the lung tissue and the thickness of the airways of mice was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical staining.
There was little expression of alpha-SMA in the lung tissue of normal mice compared with the asthma model group (P < 0.05). The expressions of alpha-SMA in the group C and D decreased compared with that in group B (P < 0.01), but no significant difference (P > 0.05) was observed between group C and D. The WAt/Pbm, WAi/Pbm, and WAm/Pbm were significantly increased in the asthma group compared with that in normal group (P < 0.05), and the WAt/Pbm, WAi/Pbm, and WAm/Pbm were decrased in the group compared with that of group B (P < 0. 01), the wAm/Pbm was decreased in the group C (P < 0. 05).
Over expression of alpha-SMA in asthmatic lung tissue is closely related to the onset of asthmatic. GABAAR antagonist bicuculline could inhibit the expression of alpha-SMA and alpha-SMA mRNA and alleviate airway remodeling with equivalent potency of inhaled corticosteroid. Our data suggest that GABAAR involve in the pathogenesis of asthmatic airway remodeling by upregulating the expression of alpha-SMA inducing the airway smooth muscle constriction and hyperplasia.
观察选择性γ-氨基丁酸(GABA)受体拮抗剂荷包牡丹碱对慢性哮喘大鼠肺组织α-平滑肌肌动蛋白(α-SMA)表达的影响,探讨荷包牡丹碱在哮喘小鼠气道重塑中的作用。
将40只BALB/c小鼠随机分为四组:对照组(A组)、哮喘模型组(B组)、荷包牡丹碱组(C组)和荷包牡丹碱联合布地奈德组(D组)。通过卵清蛋白致敏和激发建立哮喘模型。采用半定量逆转录-聚合酶链反应(RT-PCR)和免疫组织化学染色检测小鼠肺组织中α-SMA的表达及气道厚度。
与哮喘模型组相比,正常小鼠肺组织中α-SMA表达较少(P<0.05)。C组和D组α-SMA的表达较B组降低(P<0.01),但C组和D组之间差异无统计学意义(P>0.05)。与正常组相比,哮喘组的气道壁厚度/支气管壁厚度(WAt/Pbm)、气道上皮厚度/支气管壁厚度(WAi/Pbm)和气道肌层厚度/支气管壁厚度(WAm/Pbm)显著增加(P<0.05),与B组相比,C组和D组的WAt/Pbm、WAi/Pbm和WAm/Pbm降低(P<0.01),C组的WAm/Pbm降低(P<0.05)。
哮喘肺组织中α-SMA的过度表达与哮喘的发病密切相关。GABA A受体拮抗剂荷包牡丹碱可抑制α-SMA及其mRNA的表达,并减轻气道重塑,其效力与吸入性糖皮质激素相当。我们的数据表明,GABA A受体通过上调α-SMA的表达,诱导气道平滑肌收缩和增生,参与哮喘气道重塑的发病机制。