调补肺肾三法对慢性阻塞性肺疾病稳定期大鼠肺与肠道炎症指标的影响  

Effects of three Tiao-Bu Fei-Shen therapies on lung and intestinal inflammation indexes in rats with stable chronic obstructive pulmonary disease

作　　者：轩银霜 李亚[2] 卞晴晴 毛静[1] 李晓俊[1] 李素云[3,4] XUAN Yinshuang;LI Ya;BIAN Qingqing;MAO Jing;LI Xiaojun;LI Suyun(Henan University of Chinese Medicine,Zhengzhou 450046,China;Chinese Medicine Pharmacology(Respiratory)Laboratory,the First Affiliated Hospital of Henan University of Chinese Medicine Henan Key Laboratory of TraditionalChinese Medicine for the Prevention and Treatment of Respiratory Diseases,Zhengzhou 450000;Respiratory Departmentof the First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000;Co-constructionCollaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan&Education Ministry ofP.R.China,Henan University of Chinese Medicine,Zhengzhou 450046)

机构地区：[1]河南中医药大学,郑州450046 [2]河南中医药大学第一附属医院中心实验室中药药理(呼吸)实验室河南省呼吸病防治中医药重点实验室,郑州450000 [3]河南中医药大学第一附属医院呼吸科,郑州450000 [4]河南中医药大学呼吸疾病中医药防治省部共建协同创新中心,郑州450046

出　　处：《中国实验动物学报》2023年第7期888-895,共8页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家重点研发计划项目(2018YFC1704800,2018YFC1704801);国家自然科学基金(81904116);省级科技研发计划联合基金项目(222301420081);河南省高等学校重点科研项目(23B360005)。

摘　　要：目的探讨调补肺肾三法对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)稳定期大鼠肺与肠道IL-6、IL-33和IFN-γ的调控。方法将60只SD大鼠随机分为空白(Control)组、COPD模型(Model)组、补肺健脾(Bufei Jianpi,BJ)组、补肺益肾(Bufei Yishen,BY)组、益气滋肾(Yiqi Zishen,ZS)组和氨茶碱(aminophylline,Am)组。第1-8周,采用香烟烟雾暴露联合脂多糖(lipopolysaccharide,LPS)滴注法制备稳定期COPD大鼠模型,对应给予生理盐水、补肺健脾方、补肺益肾方、益气滋肾方、氨茶碱灌胃4周,于第13周灌胃周期结束后取材。光镜下观察肺与结肠组织形态学改变,采用免疫组化法(IHC)对肺与结肠组织中白细胞介素(interleukin,IL)-6、IL-33、干扰素(interferon,IFN)-γ蛋白进行定位与半定量观察。结果与Control组相比,Model组大鼠不仅支气管周围与肺泡腔出现大量炎症细胞及炎性渗出,结肠黏膜也出现了大量炎症细胞浸润,肺和结肠IL-6、IL-33和IFN-γ水平明显升高(P<0.05,P<0.01);与Model组相比,各治疗组不仅支气管和肺泡炎症细胞浸润减少,而且结肠黏膜炎症细胞也出现减少,肺与结肠中IL-33和IFN-γ、结肠IL-6水平均明显降低(P<0.05,P<0.01),BY、ZS、Am组肺IL-6水平显著降低(P<0.01)。肺IL-6与结肠IL-6水平呈正相关,肺IL-33与结肠IL-33水平呈正相关,肺IFN-γ和结肠IFN-γ水平呈正相关。结论调补肺肾三法均可以改善慢性阻塞性肺疾病稳定期大鼠肠道功能障碍,其机制可能与抑制肺与结肠中IL-6、IL-33和IFN-γ的释放,降低肺与肠道炎症反应有关。Objective To investigate the effects of three Tiao-Bu Fei-Shen therapies on interleukin(IL)-6,IL-33,and interferon(IFN)-γin the lung and intestines of rats with stable chronic obstructive pulmonary disease(COPD).Methods Sixty Sprague-Dawley rats were divided randomly into blank(Control),COPD model(Model),Bufei Jianpi(BJ),Bufei Yishen(BY),Yiqi Zishen(ZS),and aminophylline(Am)groups.A stable COPD rat model was established by cigarette-smoke exposure combined with lipopolysaccharide nasal drip in the first 8 weeks.The model rats were given normal saline,Bufei Jianpi Formula,Bufei Yishen Formula,Yiqi Zishen Formula,or aminophylline by gavage for 4 weeks.Morphological changes in the lung and colon were observed by light microscopy,and IL-6,IL-33,and IFN-γprotein levels in lung and colon tissues were localized and analyzed semi-quantitatively by immunohistochemistry.Results Rats in the model group had more inflammatory cells and inflammatory exudates around the bronchi and alveolar spaces compared with control rats,and also had more inflammatory cell infiltration in the colon mucosa and significantly increased levels of IL-6,IL-33,and IFN-γin the lung and colon tissues(P<0.05,P<0.01).Bronchial and alveolar inflammatory cell infiltration and colonic mucosal inflammatory cells were decreased in all treatment groups compared with the model group.IL-33 and IFN-γin the lung and colon and IL-6 in the colon were significantly decreased(P<0.05,P<0.01),and IL-6 in the lung was significantly reduced in the BY,ZS,and Am groups(P<0.01).There were positive correlations between lung IL-6 and colon IL-6,lung IL-33 and colon IL-33,and lung IFN-γand colon IFN-γlevels.Conclusions The three tested Tiao-Bu Fei-Shen therapies can reduce intestinal dysfunction in COPD rats.The mechanism may be related to inhibition of the release of IL-6,IL-33,and IFN-γin lung and colon tissues,and reducing the inflammatory reaction between the lung and intestine.

关 键 词：调补肺肾三法 慢性阻塞性肺疾病 肠道功能障碍 炎症介质 肺与大肠相表里 

分 类 号：Q95-33[生物学—动物学]