通肺络补宗气方对肺纤维化大鼠肺功能、MMP9/TIMP1平衡及FN、Col Ⅳ表达的影响  

Effects of Tongfeiluo Buzongqi Prescription on Pulmonary Function, MMP9/TIMP1 Balance and Expression of FN and ColIV in Rats with Pulmonary Fibrosis

作　　者：任培中 苗青[2] 杨斌[2] 范艺龄 樊茂蓉[2,3] REN Pei-zhong;MIAO Qing;YANG Bin;FAN Yi-ling;FAN Mao-rong(Third Affiliated Hospital Beijing University of Chinese Medicine,Beijing 100029,China;Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China;Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学第三附属医院,北京100029 [2]中国中医科学院西苑医院,北京100091 [3]北京中医药大学,北京100016

出　　处：《中国中医基础医学杂志》2020年第2期181-184,202,共5页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：北京市科技计划课题(Z131107002213053)-肺纤通方提高特发性肺间质纤维化患者活动耐力的临床研究;北京市自然科学基金资助项目(7162168)-基于mTOR/p70S6K通络探讨通肺络补宗气方治疗肺纤维化的作用机制;国家自然科学基金项目(81774297)-基于TGF-β1/Snail和Wnt/β-catenin信号通路介导上皮细胞间质转化探讨补肾通络方对肺纤维化大鼠的抑制作用。

摘　　要：目的:观察通肺络补宗气方对肺纤维化大鼠肺功能、基质金属蛋白酶9(MMP9)/基质金属蛋白酶抑制剂1(TIMP1)平衡及纤维连接蛋白(FN)、Ⅳ型胶原(ColⅣ)的影响。方法:健康雄性SD大鼠96只,按随机数字表法分为空白组、模型组、中药初、中、后期干预组和西药初、中、后期干预组,中药各组给予通肺络补宗气方灌胃,西药各组给予N-乙酰半胱氨酸灌胃,均连续给药90 d。实验第19周检测各组大鼠肺功能相关指标变化以及肺组织中FN、ColⅣ、MMP9和TIMP1蛋白表达水平。结果:与空白组比较,模型大鼠肺功能FVC、Cdyn明显降低,肺组织中FN、ColⅣ、MMP9和TIMP1表达水平明显升高;与模型组比较,中药初、中期干预组大鼠肺功能Cdyn明显升高(P<0.05),中西药各干预组大鼠FN、ColⅣ和TIMP1表达水平明显降低,中药初期干预组大鼠MMP9表达水平明显降低。结论:通肺络补宗气方可调节MMP9/TIMP1失衡,减少FN、ColⅣ的过度沉积,进而改善大鼠肺功能,抑制大鼠肺纤维化的发生发展。Objective:To observe the effect of Tongfeiluo Buzongqi Formula on pulmonary function, balance of MMP9/TIMP1 and the expression level of FN and Col IV in pulmonary fibrosis rats. Methods:96 healthy male SD rats were randomly divided into blank group, model group, early traditional Chinese medicine(TCM)-treated group, medium-term TCM-treated group, late TCM-treated group, early western medicine(WM)-treated group, medium-term WM-treated group and late WM-treated group. Model rats were endotracheally instillated with bleomycin. The TCM-treated groups were given the decoction of Tongfeiluo Buzongqi Formula, and the WM-treated groups were given the N-acetylcysteine solution. 19-weeks later, All rats were sacrificed after the lung function indexes measure.Protein expressions of FN and Col IV in lung tissues were evaluated by Immunohistochemistry,while the expressions of MMP9 and TIMP1 were evaluated by Western blotting. Results: The lung function indexes levels of FVC and Cdyn in model group were significantly lower than the corresponding levels in normal group, and the protein expression levels of FN, Col IV, MMP9 and TIMP1 were significantly higher. The level of Cdyn in the early and medium-term TCM-treated groups were significantly higher than the model group. The protein expression levels of FN, Col IV and TIMP1 decreased significantly in the TCM-treated groups and WM-treated groups, and the level of MMP2 in the early TCM-treated groups were significantly lower than the model group.Conclusion: Tongfeiluo Buzongqi Formula inhibit the unbalance of MMP9/TIMP1, reduced the expressions of FN and Col IV, and improved the lung function. Treatment with Tongfeiluo Buzongqi Formula may inhibited the development of pulmonary fibrosis in rats.

关 键 词：特发性肺纤维化 通肺络补宗气方 肺功能 MMP9/TIMP1 FN ColⅣ 

分 类 号：R285.5[医药卫生—中药学]