调补肺肾三法对慢性阻塞性肺疾病稳定期大鼠模型全身和肺脏炎症反应的影响及远期效应(英文)

Long-term effects of Tiaobu Feishen therapies on systemic and local inflammation responses in rats with stable chronic obstructive pulmonary disease

目的:评价调补肺肾(补肺健脾、补肺益肾、益气滋肾)三法对慢性阻塞性肺疾病(chronic obstructive pulmonarydisease,COPD)稳定期大鼠全身和肺脏局部炎症反应的影响及远期效应。方法:将大鼠随机分为6组:对照组、模型组、补肺健脾组、补肺益肾组、益气滋肾组和氨茶碱组。除对照组外,采用香烟熏吸联合细菌感染法制备COPD稳定期大鼠模型。于第9周分别以补肺健脾方、补肺益肾方、益气滋肾方和氨茶碱灌胃至第20周,于20、32周分批取材,观察外周血白细胞计数和中性粒细胞比率及血清、支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)和肺组织白细胞介素1β(interleukin-1β,IL-1β)、IL-6、IL-8、IL-10、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、可溶性 TNF受体Ⅱ(solubletumor necrosis factor receptorⅡ,sTNFR2)的水平。结果:各组外周血白细胞计数和中性粒细胞比率比较,差异无统计学意义(P>0.05)。20周时模型组BALF中白细胞计数较对照组明显升高(P<0.01),3个中药组及氨茶碱组均较模型组显著降低(P<0.01),其中补肺健脾组白细胞计数明显低于氨茶碱组(P<0.05);第32周,3个中药组的 BALF中白细胞计数较氨茶碱组明显降低(P<0.05,P<0.01),而3个中药组间比较,差异无统计学意义(P>0.05)。第20和32周,模型组血清和肺组织IL-1β、IL-6、IL-8、IL-10、TNF-α、sTNFR2含量,BALF中IL-8、IL-10、TNF-α水平均较对照组显著升高(P<0.05,P<0.01);3个中药组上述因子均较模型组明显降低(P<0.05,P<0.01),其中3个中药组血清、BALF和肺组织中细胞因子水平较氨茶碱组降低,而以血清和BALF改变明显(P<0.05,P<0.01)。第32周外周血清和BALF、肺组织炎症因子表达与20周时比较,差异无统计学意义。结论:补肺健脾、补肺益肾和益气滋肾中药可显著降低 COPD稳定期大鼠全身和肺脏局部的炎症反应,且具有良好的远期效应。

OBJECTIVE： To evaluate the influence and long-term effects on systemic and local inflammation responses in rat with stable chronic obstructive pulmonary disease （COPD） treated with traditional Chinese medicine （TCM） for regulating and invigorating the lung and kidney, including invigorating the lung and spleen （Bufei Jianpi） therapy, supplementing the lung and kidney （Bufei Yishen） therapy, and nourishing qi and kidney （Yiqi Zishen） therapy. METHODS： Rats were randomly divided into six groups： control, model, aminophyline, Bufei Jianpi, Bufei Yishen and Yiqi Zishen groups. The stable COPD model of rat was duplicated by cigarette smoke inhalations and bacterial infection. From the ninth week, the rats with stable COPD were treated with Bufei Jianpi, Bufei Yishen, Yiqi Zishen granules or aminophyline respectively until the 20th week. Half of the animals were sacrificed at the 20th or 32nd week respectively. The leukocyte count and neutrophil percentage in peripheral blood and bronchoalveolar lavage fluid （BALF） were measured; levels of interleukin （IL）-8, IL-10 and tumor necrosis factor-α （TNF-α） in BALF, and levels of IL-l13, IL-6, IL-8, IL-10 and TNF-α and soluble tumor necrosis factor receptor Ⅱ （sTNFR2） in serum and lungs were detected by enzyme-linked immunosorbent assay or immunohistochemical method, RESULTS： There were no statistical differences in leukocyte count and neutrophil percentage in peripheral blood among six groups （P〉0.05）. At the 20th week, leukocyte count in BALF was higher in the model group than in the control group （P〈0.01）, and was lower in the three TCM groups and the aminophyline group than in the model group （P〈0.05, P〈0. 01）, and that of the Bufei Jianpi group was lower than the aminophyline group （P〈0.01）; while at the 32nd week, leukocyte count in BALF of the three TCM groups decreased and was lower than that of the aminophyline group （P〈0.05, P〈0.01）. At the 20th and 32nd weeks, levels of IL-1β, IL- 6, IL-8, IL-10, TNF-α and sTNFR2 in serum and lungs, and IL-8, IL-10 and TNF-α in BALF of the model group increased, which were higher than those in the control group （P〈0. 05, P〈. 01）, the mentioned cytokines were decreased in the three TCM groups compared with the modelgroup （P〈0.05, P〈0.01）, and were also lower in serum and BALF of the three TOM groups than those of the aminophyline group （P〈0. 05, P〈0.01）. Expressions of cytokines in lung tissues were depressed in the three TCM groups as compared to those in the aminophyline group. There was no statistical difference on expressions of the mentioned cytokines either in serum and BALF or in the lungs between week 32 and week 20. CONCLUSION： The Bufei Jianpi, Bufei Yishen and Yiqi Zishen therapies can significantly reduce the systemic and local inflammation responses in rats with stable COPD, and have evident long-term effects.