College of Preclinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
College of Preclinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Chin J Nat Med. 2013 Nov;11(6):638-44. doi: 10.1016/S1875-5364(13)60074-6.
To evaluate the effect of Qi'ao Deocoction (QAD) on the inflammation and hyperresponsiveness of asthma mice.
120 Balb/C mice were randomly divided into six groups: normal group, model group, dexamethasone group, high dose QAD group, medium dose QAD group and low dose QAD group. The asthma model was reproduced in Balb/C mice sensitized by ovalbumin, challenged by OVA and LPS. The mice of the normal group were sensitized, challenged and intranasally instilled by PBS. On day 28-34, 6.7, 13.4 and 26.8 g · kg(-1) Qi'ao Decoction were administrated; 0.002 4 g · kg(-1) dexamethasone solution was given to the dexamethasone group; normal and model groups were given the same amount of normal saline. Bronchoalveolar lavage fluid, airway hyperresponsiveness, lung histopathology and cytokines were then collected and analyzed.
Compared with normal group, total cellular score, the number of macrophages, lymphocytes, eosinophils and neutrophils of model group significantly increased (P < 0.01). Compared with model group, the administration of dexamethasone induced a significant decrease in eosinophils and neutrophils (P < 0.05, P < 0.01). The number of eosinophils, which plays an important role in airway inflammatory reaction of asthma, of the three QAD groups all decreased (P < 0.01). RL before and after Ach (5 mg · mL(-1)) stimulation in the model group both overtook that in the normal group (P < 0.01). Compared with model group, dexamethasone group, high dose QAD group, medium dose QAD group and low dose QAD group groups all had significantly lower RL before and after Ach stimulation (P < 0.01). Normal pulmonary histopathology was found in the normal group. In the model group, mice exhibited marked increases in inflammatory cell infiltration, mostly including neutrophils and macrophages, perivascular inflammation and thickened alveolus wall (P < 0.01). Dexamethasone application mitigated inflammation around the bronchi (P < 0.05). These histopathological changes were ameliorated in the three decoction groups (P < 0.01, P < 0.05). In addition, alveolus and airway wall lesions of medium dose QAD group and high dose QAD group were reduced, the number of inflammatory cells infiltrated around the walls decreased, no clear degeneration of bronchial epithelial cells was found, and exudates in bronchi declined in different degrees. Compared with normal group, IFN-γ and IL-12 of model group significantly decreased, while IL-4 increased, showing statistic difference (P < 0.05). Compared with model group, IFN-γ and IL-12 level of dexamethasone group went up too, but IL-4 declined (P < 0.05). The level of IFN-γ of medium dose QAD group and high dose QAD group both increased; IL-4 and IL-12 of medium dose group were found significant differences (P < 0.05); but none of the cytokines of low dose QAD group showed statistical significance (P > 0.05).
QAD can significantly inhibit airway inflammation and airway hyperresponsiveness of mice with severe asthma induced by ovalumin and lipopolysaccharide, adjust the balance of cytokines, and improve lung histopathological condition. So, it exhibits great effect on severe asthma.
观察芪翘地黄汤对哮喘小鼠炎症和气道高反应性的影响。
120 只 Balb/C 小鼠随机分为 6 组：正常组、模型组、地塞米松组、芪翘地黄汤高剂量组、芪翘地黄汤中剂量组、芪翘地黄汤低剂量组。卵清蛋白致敏、卵清蛋白和脂多糖激发复制哮喘小鼠模型，正常组用 PBS 滴鼻激发。第 28-34 天，分别给予 6.7、13.4、26.8 g·kg(-1)芪翘地黄汤；地塞米松组给予 0.002 4 g·kg(-1)地塞米松溶液；正常组和模型组给予等容量生理盐水。收集支气管肺泡灌洗液，检测气道高反应性，观察肺组织病理变化，并检测细胞因子。
与正常组比较，模型组肺泡灌洗液总细胞计数、巨噬细胞、淋巴细胞、嗜酸性粒细胞和中性粒细胞数明显增加（P < 0.01）。与模型组比较，地塞米松组和芪翘地黄汤各剂量组嗜酸性粒细胞和中性粒细胞数均减少（P < 0.05，P < 0.01），其中芪翘地黄汤中、高剂量组和地塞米松组的气道炎症反应中起重要作用的嗜酸性粒细胞数均明显减少（P < 0.01）。与正常组比较，模型组乙酰胆碱（5 mg·mL(-1))激发前后 RL 值均明显增加（P < 0.01）。与模型组比较，地塞米松组、芪翘地黄汤各剂量组乙酰胆碱激发前后 RL 值均明显降低（P < 0.01）。正常组肺组织病理形态无明显改变，模型组肺组织可见明显的炎症细胞浸润，以中性粒细胞和巨噬细胞为主，伴小血管周围炎及肺泡壁增厚（P < 0.01）。地塞米松组炎症浸润减轻（P < 0.05）。芪翘地黄汤各剂量组炎症浸润减轻（P < 0.01，P < 0.05）。此外，中、高剂量组及地塞米松组的肺泡和气道壁病变减轻，壁周炎症细胞浸润减少，支气管上皮细胞变性不明显，支气管内渗出物减少。与正常组比较，模型组干扰素-γ和白细胞介素-12 明显降低，白细胞介素-4 明显升高（P < 0.05）；与模型组比较，地塞米松组和芪翘地黄汤各剂量组干扰素-γ和白细胞介素-12 明显升高，白细胞介素-4 明显降低（P < 0.05）。中、高剂量组的干扰素-γ水平升高，中剂量组白细胞介素-4 和白细胞介素-12 差异有统计学意义（P < 0.05），但低剂量组的细胞因子差异均无统计学意义（P > 0.05）。
芪翘地黄汤可显著抑制卵清蛋白和脂多糖诱导的哮喘小鼠气道炎症和气道高反应性，调节细胞因子平衡，改善肺组织病理状态，对重症哮喘有较好的治疗作用。
