天龙咳喘灵对慢性哮喘小鼠气道重塑的影响

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目的探讨中药验方天龙咳喘灵水煎剂治疗哮喘气道高反应的可能机制。方法实验设四组,盐水对照组,哮喘模型组,天龙咳喘灵治疗组和布地奈德(BUD)治疗组。小鼠经常规鸡卵清蛋白(OVA)致敏后连续18d给予1%的OVA雾化吸入激发。末次激发后24h和96h,利用体积描记仪动态观察各组小鼠气道反应性,24h-时间点取部分小鼠进行肺泡灌洗,观察肺泡灌洗液(BALF)中细胞总数和细胞分类,剩余小鼠完成96h-时间点气道反应性检测后与上述同样处理,并分离小鼠右肺制备组织切片进行病理分析。结果末次激发后24h或96h,与盐水对照组相比,OVA-哮喘组小鼠气道反应性显著升高(P<0.01),相应BALF中细胞总数和嗜酸粒细胞比例也明显增加;天龙咳喘灵治疗组小鼠在24h时间点气道反应性较未治疗哮喘组无明显差别,BALF中细胞总数和嗜酸性粒细胞比例亦较正常对照组增加(P<0.01),但在激发后96h气道反应性基本回到正常水平;相比之下,BUD治疗组小鼠在24h时间点气道反应性显著低于哮喘组或天龙咳喘灵治疗组(P<0.01),但却在96h后气道反应性反弹上升,显著高于正常对照及天龙咳喘灵治疗组(P<0.01),此时各组细胞总数和嗜酸粒细胞比例均已明显下降,且BUD治疗组仍低于天龙咳喘灵治疗组(P<0.01)。肺组织病理切片显示哮喘组和BUD治疗组上皮下基底膜层明显增厚,α-SMA免疫染色显著增强,而天龙咳喘灵治疗组气道上皮下未见明显改变,α-SMA表达水平与盐水对照组无显著差别。结论不同于表面激素的抗炎效应,天龙咳喘灵水煎剂能有效防治慢性哮喘小鼠模型气道高反应性,可能主要是通过抑制肌纤维母细胞激活的抗重构作用机制。 Objective To investigate the possible mechanism of traditional Chinese medicine prescription Tianlong Kechuanling decoction in treating asthmatic airway hyperresponsiveness. Methods The experiment was divided into four groups: saline control group, asthma model group, Tianlongkechuanling treatment group and budesonide (BUD) treatment group. Mice were stimulated with 1% OVA atomized inhalation for 18 consecutive days after sensitization with conventional chicken ovalbumin (OVA). After 24h and 96h after the last challenge, the airway responsiveness of mice in each group was observed dynamically by plethysmograph, and some mice were taken alveolar lavage at 24h-time point to observe the total number of cells and cell classification in BALF, The remaining mice completed 96h-time airway reactivity test the same treatment as above, and isolated from the right lung of mice to prepare tissue sections for pathological analysis. Results Compared with the saline control group, the airway responsiveness in OVA-asthmatic mice was significantly increased (P <0.01) at 24 h or 96 h after the last challenge, and the total number of cells and eosinophils in the corresponding BALF also increased significantly. Compared with the untreated asthmatic group, there was no significant difference in the airway responsiveness between the mice in Kechuanling group and untreated group at 24h, and the total number of cells and the ratio of eosinophils in BALF also increased compared with the normal control group (P <0.01) 96h airway reactivity returned to normal levels; compared with the BUD treatment group mice at 24 hours airway reactivity was significantly lower than the asthma group or Tianlongkechuanling treatment group (P <0.01), but in After 96h, the rebound of airway increased, which was significantly higher than that of normal control group and Tianlongkechuanling treatment group (P <0.01). At this time, the total number of cells and eosinophil percentage in each group were significantly decreased, and the BUD treatment group was still low Yu Longke Chuanling treatment group (P <0.01). Lung histopathology showed that the epithelial basement membrane thickening and α-SMA immunostaining were significantly increased in the asthma group and the BUD treatment group, while there was no significant change in the Tianlongkechuanling treatment group, the expression level of α-SMA and saline The control group no significant difference. Conclusion Unlike the anti-inflammatory effects of surface hormones, Tianlong Kechuanling decoction can effectively prevent and treat airway hyperresponsiveness in a mouse model of chronic asthma, possibly by inhibiting the anti-remodeling mechanism of myofibroblasts activation.
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