淫羊藿对哮喘大鼠气道高反应性的影响

Effects of Epimedii Folium on Airway Hyperresponsiveness in Rat Asthma Model

摘要:

目的: 探讨淫羊藿对哮喘大鼠模型气道高反应性的影响. 方法: 将SD大鼠60只随机分为正常对照组、哮喘模型组、地塞米松组、及淫羊藿低、中、高剂量组,每组10只.实验开始第0天,大鼠ip含卵蛋白100μg和氢氧化铝100 mg的生理盐水溶液,第14天起予1%卵蛋白激发3周,第35天起2%卵蛋白激发1周.治疗组第14天起给予低、中、高剂量淫羊藿0.25,0.5,1 g·kg^-1,或地塞米松1 mg·kg^-1,每天1次,连续4周.正常组与模型组用等量生理盐水代替.采用Buxco肺功能仪有创法检测气道反应性;ELISA法检测肺泡灌洗液细胞因子干扰素(INF)-γ,白介素(IL)-4,IL-5,IL-13,IL-10,IL-6,肿瘤坏死因子(TNF)-α及转化生长因子-β(TGF-β);肺组织HE,PAS及Masson三色染色评价观察小鼠肺组织炎症、气道黏液分泌水平及气道壁周围胶原沉积水平. 结果: 与正常组相比,模型组气道阻力(R_L)明显升高,肺顺应性(C_dyn)明显降低(P<0.01);肺泡灌洗液IL-4,IL-5,IL-13,TGF-β₁和TNF-α水平显著升高(P<0.05, P<0.01),而INF-γ水平显著下降(P<0.05);气道炎症指数、气道黏液评分、及气道周围胶原评分显著升高(P<0.01).与模型组相比,淫羊藿低、中、高剂量组可不同程度降低气道阻力,改善肺顺应性(P<0.05, P<0.01);淫羊藿高剂量组可显著降低哮喘模型组肺泡灌洗液中IL-4(P<0.05),IL-5和IL-13水平(P<0.01);中剂量组可显著降IL-5和IL-13水平(P<0.05,P<0.01),且能显著升高IL-10水平(P<0.05);低剂量组可显著降低IL-5水平(P<0.05);淫羊藿中、高剂量治疗组气道炎症指数、气道黏液评分,以及气道周围胶原面积显著降低(P<0.05,P<0.05). 结论: 淫羊藿可改善哮喘模型气道高反应性,这与其抑制气道炎症,及改善气道重塑相关.

Abstract:

Objective: To evaluate effects of Epimedii Folium on airway hyperresponsiveness in rat asthma. Method: Sixty SD rats were randomly divided into 6 groups, including the normal group, asthma model group, dexamethasone group, and three Epimedii Folium groups at dose of 2.5, 5.0, 10.0 g· kg^-1 with 10 rats in each group. A rat model of asthma was developed by ovalbumin OVA sensitization with 100 mg of OVA mixed with 100 mg aluminum hydroxide on day 0, followed by exposing to aerosolized OVA for 4 weeks. Airway reactivity was measured by Buxco's modular and invasive system. Interleukin[interferon-γ(INF-γ), interleukin(IL) -4, IL-5, IL-6, IL-13, tumor necrosis factor-α(TNF-α) and transforming growth factor-β(TGF-β₁)] levels in the bronchoalveolar lavage fluid(BALF) supernatant were analyzed by enzyme-linked immunosorhent assay(ELISA). Lung tissues were examined to evaluate the severity of inflammatory cell infiltration, airway mucus expression, and collagen deposition. Result: Compared with the normal group, OVA-expose significantly increased airway resistance of rats(R_L) (P<0.01), decreased lung dynamic compliance (C_dyn) (P<0.01), elevated levels of IL-4, IL-5, IL-13, TGF-β₁ and TNF-α, but reduced INF-γ(P<0.05, P<0.01)in the BALF,and marked increase of inflammatory cells, mucus production and collagen deposition in lung tissues (P<0.01). Compared with the model group, epimedium at the dose of 2.5, 5.0,10.0 g· kg^-1 significantly reduced R_L,improved C_dyn (P<0.05). Epimedii Folium dose-dependently inhibited the IL-4, IL-5, and IL-13 in BALF (P<0.05, P<0.01). Histological studies showed that Epimedii Folium at the dose of 5.0, 10.0 g· kg^-1 markedly inhibited airway inflammation, mucus production and collagen deposition in lung tissues (P<0.05, P<0.01). Conclusion: Epimedii Folium can significantly inhibit airway hyperresponsiveness, which is associated with its alleviation on airway inflammation and remodeling.