基于“肺肠同治”理论探讨肛滴平喘汤对慢性阻塞性肺病大鼠肺功能及白细胞介素-4、白细胞介素-12的影响

Based on the Theory of Treatment of Lung and Intestine to Discuss the Effects of Gangdi Pingchuan Decoction(肛滴平喘汤) on Lung Function and IL-4 and IL-12 in COPD Rats

目的观察肛滴平喘汤对慢性阻塞性肺病(COPD)大鼠肺功能及肺组织白细胞介素-4(IL-4)、白细胞介素-12(IL-12)的影响。方法选取体质量约250 g的雄性SD大鼠60只,随机选出10只作为正常组,其余50只大鼠经香烟烟熏及气管滴注脂多糖(LPS)造成COPD模型,将造模成功的大鼠随机分为模型组、西药组、中药高剂量组、中药中剂量组、中药低剂量组。西药组给予醋酸泼尼松片混悬液灌肠治疗,中药中剂量组按人鼠等效剂量换算给予肛滴平喘汤浓缩剂灌肠治疗,中药高剂量组用药量为中剂量组的2倍,中药低剂量组用药量为中剂量组的50%,正常组和模型组均给予同等剂量蒸馏水灌肠。用药4周后,观察各组大鼠一般状态,应用动物肺功能仪检测各组大鼠潮气量(VT、50%潮气量时的呼气流量(EF50)、呼气峰流速(PEF),采用HE染色法观察各组大鼠肺组织结构变化,免疫组化法检测大鼠肺组织IL-4、IL-12的表达。结果用药灌肠治疗4周后,与正常组大鼠相比,模型组大鼠细支气管管壁炎性细胞浸润,肺泡扩张膨大,部分融合;与模型组相比,西药组及中药高、中剂量组大鼠细支气管管壁炎性减轻,肺泡结构有所改善,中药低剂量组大鼠细支气管管壁炎性减轻,肺泡结构有所改善,但改善程度较其他治疗组小。与正常组相比,模型组大鼠VT、EF50、PEF均明显降低(P<0.05),与模型组相比,西药组及中药各剂量组VT、EF50、PEF均明显上升(P<0.05),中药各剂量组组间比较可见,中药高剂量组及中剂量组大鼠VT、EF50、PEF高于低剂量组(P<0.05),中药高剂量组与中剂量组比较,上述指标未见明显改变(P>0.05)。与正常组相比,模型组大鼠肺组织IL-4表达降低,IL-12表达升高(P<0.05),与模型组比较,西药组及中药各剂量组大鼠肺组织IL-4表达升高(P<0.05),西药组及中药高、中剂量组大鼠肺组织IL-12表达降低(P<0.05),中药低剂量组无明显改变(P>0.05)。结论肛滴平喘汤可调控COPD大鼠肺部炎性因子IL-4、IL-12的表达,改善大鼠肺泡结构及肺功能,有效治疗COPD,为“肺肠同治”理论指导治疗COPD提供实验依据。

Objective To observe the effects of Gangdi Pingchuan Decoction(肛滴平喘汤)on the lung function and the expression of IL-4 and IL-12 in chronic obstructive pulmonary disease rats.Methods 60 male SD rats weighing about 250 g were selected,and 10 rats were random Ly selected as the normal group.The remaining 50 rats were induced by cigarette smoking and tracheal instillation of lipopolysaccharide(LPS)to create the COPD model.Rats were random Ly divided into model group,western medicine group,Chinese medicine high-dose group,Chinese medicine middle-dose group,Chinese medicine low-dose group.The western medicine group was given enema treatment of prednisone acetate suspension,the Chinese medicine middledose group was given Gangdi Pingchuan Decoction concentrate enema according to the equivalent dose conversion of human and rat,and the dosage of the Chinese medicine high-dose group was twice that of the middle-dose group.The dosage of the Chinese medicine high and low dose group was 50%of that of the middle dose group.Both the normal group and the model group were given the same dose of distilled water enema.After 4 weeks of medication,observe the general state of each group of rats,and use animal lung function instrument to detect the tidal volume(VT)and expiratory flow at 50%tidal volume(EF50),Expiratory peak flow rate(PEF),using HE staining method to observe the changes of lung tissue structure of each group of rats,immunohistochemical method to detect the expression of IL-4 and IL-12 in rat lung tissue.Results After 4 weeks of administration,compared with the normal group,the model group had bronchiole wall infiltration of inflammatory cells,alveolar expansion and partial fusion;compared with the model group,the western medicine group and the Chinese medicine high and middle dose groups were larger Inflammation of the bronchiole wall of rats was reduced,and the alveolar structure was improved.In the low-dose group of Chinese medicine,inflammation of the bronchiole wall was reduced and the alveolar structure was improved,but the degree of improvement was smaller than that of other treatment groups.Compared with the normal group,the VT,EF50,and PEF of the model group were significantly reduced(P<0.05).Compared with the model group,the VT,EF50,and PEF of the western medicine group and each dose group of Chinese medicine were significantly increased(P<0.05).The comparison between the various groups of traditional Chinese medicine shows that the VT,EF50 and PEF of rats in the high-dose group and medium-dose group are higher than those in the low-dose group(P<0.05).The high-dose group and the medium-dose group In comparison,the above indicators did not change significantly(P>0.05).Compared with the normal group,the expression of IL-4 in the lung tissue of the model group decreased and the expression of IL-12 increased(P<0.05).Compared with the model group,the expression of IL-4 in the lung tissue of the western medicine group and each dose group of traditional Chinese medicine elevated(P<0.05),the expression of IL-12 in the lung tissue of rats in the western medicine group and the high and middle dose groups of Chinese medicine decreased(P<0.05),and there was no significant change in the low dose group of traditional Chinese medicine(P>0.05).Conclusion Gangdi Pingchuan Decoction can regulate the expression of IL-4and IL-12 in the lungs of COPD rats,improve the alveolar structure and lung function of rats,and effectively treat COPD.It provides an experimental basis for the treatment of COPD with the theory of combined treatment of lung and intestine.