摘要
目的:基于JAK/STAT通路及基质金属蛋白酶(MMPs)系统探讨六味补气胶囊改善慢性阻塞性肺疾病(COPD)肺气虚证的机制。方法:将75只大鼠随机分为正常对照组、模型对照组、六味补气组、金水宝组、脾氨肽组,每组15只。除正常对照组外,其余大鼠均采用烟熏加脂多糖气管滴入方法建立COPD肺气虚证模型。模型成功第28天给药,正常对照组、模型对照组予0.9%氯化钠溶液(0.09g·kg-1·d-1),六味补气组予六味补气胶囊(0.35g·kg-1·d-1),金水宝组予金水宝胶囊(0.495g·kg-1·d-1),脾氨肽组予脾氨肽(0.33mg·kg-1·d-1),1次/d,连续给药30d。观察各组大鼠肺组织形态学、肺功能、细胞因子、JAK/STAT通路、MMP-9及MMPs抑制剂1(TIMP1)变化。结果:与正常对照组比较,模型对照组肺组织损伤、肺功能降低,炎性因子白介素(IL)-1β、γ干扰素(IFN-γ)、IL-6升高(P<0.01),抑炎因子IL-4、IL-10降低(P<0.01);肺组织JAK1、STAT3、p-STAT3及MMP-9基因和蛋白表达升高,TIMP1基因和蛋白表达降低(P<0.05,P<0.01)。药物治疗后,与模型对照组比较,六味补气组IFN-γ、IL-6减少,JAK1、p-STAT3、MMP-9基因及蛋白表达降低,TIMP1表达升高(P<0.05,P<0.01);与金水宝组、脾氨肽组比较,六味补气组在提高COPD大鼠肺功能、降低JAK1、STAT3、p-STAT3及提高TIMP1基因蛋白表达方面优于两组(P<0.05,P<0.01)。结论:六味补气胶囊通过上调TIMP1,下调JAK1、STAT3、p-STAT3、MMP-9表达,降低炎性反应,改善COPD肺气虚证肺功能及症状体征。
Objective： To study the mechanism of Liuwei Buqi Capsule on the rat model of chronic obstructive pulmonary disease （COPD） accompanied deficiency of lung qi based on JAK/STAT pathway and matrix metalloproteinases （MMPs）. Methods： 75 rats were randomly divided into normal control group, model control group, Liuwei Buqi group, Jinshuibao group and spleen aminopeptidase group, with 15 in each group. In addition to the normal group, the rat model of COPD accompanied deficiency of Lung qi was established by smoke plus lipopolysaccharide tracheal instillation method. 28 days after the model copied, normal control group and model control group were given normal saline （0.09g. kg1. d＇t）, and the other groups were given Liuwei Buqi Capsule （0.35g. kg4. d-1）, Jinshuibao Capsules （0.495g. kg-1. d-l）, Spleen aminopeptidase （0.33mg. kg-l. d-1）, once a day for consecutive 30 days, respectively. The changes of lung histological, lung function, cytokines, JAKJSTAT pathway, MMP-9 and MMPs inhibitor 1 （TIMP1） were observed. Results： Compared with normal control group, lung tissue was damaged, and lung function reduced, while the level of intedeukin （IL）-1β, γ interferon （IFN-γ）, IL-6, JAK1, STAT3, p-STAT3, MMP-9 mRNA and protein of lung tissue increased, IL-4, IL-10, TIMP1 gene and protein decreased in the model control group （P〈0.05, P〈0.01）. Compared with the model group, the expression of IFN-γ IL-6 decreased, expression of JAK1, p-STAT3, MMP-9 gene and protein decreased, and TIMP1 gene and protein increased in the Liuwei Buqi group （P〈0.05, P〈0.01）. Compared with the Jinshuibao and spleen aminopeptidase group, lung function was increased, JAK1, STAT3, p-STAT3 protein were reduced and TIMP1 was improved in Liuwei Buqi group （P〈0.05）. Conclusion： Liuwei Buqi Capsules can reduce inflammation, improve lung function and relieve symptoms by up-regulating TIMP1, down-regulating the expression of JAK1, STAT3, p-STAT3 and MMP-9.
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2014年第5期1384-1390,共7页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金(No.81072781)~~
