摘要
目的通过观察溃疡性结肠炎(ulcerative colitis,UC)大鼠模型肺、肠组织先天免疫应答与后天免疫应答的改变及中药复方的干预作用,探讨"肺与大肠相表里"的中医学理论。方法 70只大鼠随机分为正常对照组、模型组、从肺论治组、从肠论治组及柳氮磺胺吡啶组,正常对照组10只,模型组与治疗组各15只,除正常对照组外,其余各组大鼠大鼠均用结肠黏膜致敏联合三硝基苯磺酸加50%乙醇灌肠的免疫复合法制UC大鼠模型,进行药物(从肺论治方、从肠论治方及柳氮磺胺吡啶)灌胃干预,治疗后4周杀检取材,采用放射免疫方法检测肺、肠组织和血清中肿瘤坏死因子-α(TNF-α)、白介素-8(IL-8)的含量,采用ELISA法检测血清Med CAM-1含量;采用Real time-PCR法检测肺、肠组织中Toll样受体4(TLR4)、核转录因子-κB(NF-κB)、中性粒细胞移动抑制因子(MIF)、黏膜地址素黏附分子-1(Mad CAM-1)基因转录水平的改变。结果本UC模型肺组织中TNF-α含量,TLR4 mRNA,IL-8含量,MIF mRNA,Mad CAM-1 mRNA表达均较正常对照组明显升高(P<0.01);与模型组比较,从肺论治方、从肠论治方肺组织中TNF-α含量,TLR4 mRNA,IL-8含量,MIF mRNA,Mad CAM-1 mRNA表达水平均明显降低(P<0.01);模型组肠组织中Mad CAM-1 mRNA表达较正常对照组明显升高(P<0.01),TNF-α含量,NF-κBmRNA表达明显下降(P<0.05,P<0.01);与模型组比较,各治疗组肺、肠组织中Mad CAM-1 mRNA均显著下降(P<0.05,P<0.01)。模型组血清中TNF-α含量较正常对照组明显升高(P<0.05);与模型组比较,从肺论治方、从肠论治方均能明显降低血清中TNF-α含量(P<0.05,P<0.01)。结论本UC模型肠组织发生损伤的机制主要与后天免疫应答激活相关,同时伴有先天免疫应答功能降低;肺组织发生损伤的机制与先天免疫应答、后天免疫应答均相关;从肺论治、从肠论治均能明显改善肺、肠组织免疫失衡。以上说明了肺、肠组织的特殊联系,为"肺与大肠相表里"的中医学理论提供了实验依据。
Objective To explore Chinese medical theory of Fei and Dachang being interior-exteriorly correlated by observing changes of inherent immune response and acquired immune response in the lung tissue and the intestinal tissue of ulcerative colitis（ UC） model rats and the intervention of Chinese compounds（ CM）. Methods Seventy rats were randomly divided into 5 groups,i. e.,the normal control group（n = 10）,the model group（n = 15）,the treatment 1 group（n = 15,treated from Fei）,the treatment 2 group（n = 15,treated from the intestine）,and the Western medicine（ WM） group [n =15,treated with Sulfasalazine（ SASP）. Except those in the normal control group,the UC rat model was prepared by allergizing colon mucosa combined with TNBS-alcohol（ 50%） enema,and then intervened by medication（ treated with CM complex prescription of treatment from lung,CM complex prescription of treatment from intestine,and SASP）. After intragastric administration for 4 weeks,rats were sacrificed and samples taken. The expression of tumor necrosis factor α（ TNF-α） and IL-8 contents in the lung tissue,the intestinal tissue,and the serum were detected by radioimmunoassay. Serum Med CAM-1contents were detected using ELISA. Changes of the expression of Toll-like receptor 4（ TLR4）,nuclear factor κB（ NF-κB）,neutrophil migration inhibition factor（ MIF）,mucosal addressin cell adhesion molecule-1（ Mad CAM-1） mRNA in the lung tissue and the intestinal tissue were detected by real time PCR. Results Compared with the normal control group,the expression levels of TNF-α,TLR4 mRNA,IL-8,MIF mRNA,and Mad CAM-1 mRNA obviously increased in the model group（P 〈 0. 01）. Compared with the model group,the expression levels of TNF-α,TLR4 mRNA,IL-8,MIF mRNA,and Mad CAM-1 mRNA obviously decreased in the treatment 1 and 2 groups（P 〈 0. 01）. The expression of Mad CAM-1 mRNA in the intestinal tissue was obviously higher in the model group than in the normal control group（P 〈 0. 01）,while the expressions of TNF-α and NF-κB mRNA was obviously lower in the model group than in the normal control group（P 〈 0. 05,P 〈 0. 01）. Compared with the model group,the expression of Mad CAM-1 mRNA all significantly deceased in each treatment group（P 〈 0. 05,P 〈 0. 01）. Serum TNF-α contents were higher in the model group than in the normal control group（P 〈0. 05）. Compared with the model group,serum TNF-α contents could be lowered in the treatment 1 and 2 groups（P 〈0. 05,P 〈 0. 01）. Conclusions The main mechanisms of the intestinal injury in this UC model might be related with activation of acquired immune response,accompanied with lowered functions of inherent immune response. The main mechanisms of the lung injury in this UC model might be related acquired immune response and inherent immune response. Treatment from Fei and treatment from Dachang both could obviously improve the immunodissonance of Fei and Dachang,indicating the special relation between the lung tissue and the intestinal tissue,thus providing experimental evidence for Chinese medical theory of Fei and Dachang being interior-exteriorly correlated.
出处
《中国中西医结合杂志》
CAS
CSCD
北大核心
2015年第1期63-70,共8页
Chinese Journal of Integrated Traditional and Western Medicine
基金
国家“973计划”资助项目(No.2009CB522705)
关键词
溃疡性结肠炎
先天免疫应答
后天免疫应答
中医治疗
肺与大肠相表里
ulcerative colitis
inherent immune response
acquired immune response
Chinese medical remedy
Fei and Dachang being interior-exteriorly correlated
