文献类型：期刊文献

中文题名：泻肺汤对肺纤维化大鼠TGF-β1/Smads信号转导通路的干预研究

英文题名：Intervention of Xiefei Decoction on TGF-β1/Smads signal transduction pathway in rats with pulmonary fibrosis

作者：安方玉[1];颜春鲁[1,2];刘永琦[1,2];骆亚莉[1];伍志伟[1];刘雪松[1];史旭锋[1];张雪[1]

第一作者：安方玉

机构：[1]甘肃中医药大学;[2]甘肃省高校重大疾病分子医学与中医药防治研究省级重点实验室

第一机构：甘肃中医药大学

年份：2018

卷号：33

期号：6

起止页码：2641

中文期刊名：中华中医药杂志

外文期刊名：China Journal of Traditional Chinese Medicine and Pharmacy

收录：CSTPCD;;北大核心:【北大核心2017】；CSCD:【CSCD2017_2018】；

基金：甘肃省科技厅自然科学基金第二批B类计划(No.2305146208);敦煌医学与转化省部共建教育部重点实验室开放基金项目(No.DHYX1213-013)~~

语种：中文

中文关键词：肺纤维化;泻肺汤;转化生长因子β1;肿瘤坏死因子α

外文关键词：Pulmonary fibrosis;Xiefei Decoction;Transforming growth factor-β 1 （TGF- β1）;Tumor necrosisfactor-α（TNF- α）

摘要：目的:观察泻肺汤对博莱霉素致肺纤维化大鼠血清转化生长因子β1(TGF-β1)和肿瘤坏死因子α(TNF-α)及肺组织Smad2/Smad7蛋白表达的影响。方法:将84只健康雄性SD大鼠随机分成6组,即正常对照组,模型组,泻肺汤低、中、高剂量组,阳性对照组,每组14只。除正常对照组外,其余各组采用气管滴注博莱霉素法制备肺纤维化大鼠模型,正常对照组气管内滴注等量0.9%氯化钠溶液,造模24h后,泻肺汤低、中、高剂量组用泻肺汤(剂量分别为10、20、40g·kg-1·d-1)灌胃,阳性对照组用醋酸泼尼松(1.8mg·kg-1·d-1)灌胃,正常对照组及模型组用等体积0.9%氯化钠溶液灌胃,第29天测定各组大鼠肺功能后处死动物,ELISA法测定血清TGF-β1和TNF-α的含量,比色分析法测定肺泡灌洗液中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,Western Blot法检测各组大鼠肺组织Smad2/Smad7蛋白的表达。结果:与正常对照组比较,模型组肺功能呼气时间(TE)、吸气末期停顿(EIP)、吸气气流高峰流速(PIF)、呼气气流高峰流速(PEF)、呼出50%气量时的流速(EF50)、每分钟通气量(MV)、潮气量(TV)、最大呼气量(EV)、肺泡通气量(AV)均显著降低,肺泡灌洗液中SOD活性显著降低,MDA含量显著升高,血清TNF-α和TGF-β1的含量均显著升高,肺组织Smad2表达水平明显升高,Smad7表达水平明显降低(P<0.01)。与模型组比较,泻肺汤各剂量组肺功能EIP、EEP、RT、TV、EV、MV、AV均显著升高,肺泡灌洗液中SOD活性显著增高,MDA含量显著降低,肺组织Smad7表达水平显著升高(P<0.05,P<0.01);同时,泻肺汤中、高剂量组EF50显著升高,且泻肺汤高剂量组TE和PEF均显著升高(P<0.05,P<0.01);而泻肺汤中、高剂量组血清TGF-β1和TNF-α的含量均显著降低,Smad2表达水平明显降低(P<0.05,P<0.01)。结论:泻肺汤可下调TGF-β1、Smad2及上调Smad7来抑制TGF-β1/Smads信号转导通路,从而发挥抗肺纤维化的作用。
Objective： To observe the effects of Xiefei Decoction on the expression of serum transforming growth factor β1（TGF-β1） and tumor necrosis factor-α（TNF-α） and Smad2/Smad7 protein in lung tissue of rat model of bleomycin induced pulmonary fibrosis. Methods： Eighty-four male SD rats were randomly divided into 6 groups： the normal control group, the model group, the low, middle and high dose group of Xiefei Decoction, and the positive control group, with 14 rats in each group. Except the normal control group, the other groups were treated with bleomycin solution by tracheal instillation to induce pulmonary fibrosis model. The normal control group was treated with 0.9% sodium chloride solution in the endotracheal drip. After 24 h, the low, middle and high dose of Xiefei Decoction was given by gavage with the dosage of 10, 20, and 40 g·kg-1·d-1. The positive control group was given by gavage with prednisone（1.8 mg·kg-1·d-1）. The normal control group and the model group were given with equal volume of 0.9% sodium chloride solution as the same way. On the twenty-ninth days, the rats were sacrified after the detection of lung function. The levels of TGF-β1 and TNF-α in serum were measured by ELISA. The activity of superoxide dismutase（SOD） and the levels of malondialdehyde（MDA） in alveolar lavage were measured by colorimetric analysis. The expression of Smad2/Smad7 protein in lung tissue of each group was detected by Western Blot. Results： Compared with the normal control group, the TE, EIP, PIF, PEF, EF50, MV, TV, EV, AV levels and the SOD activity were decreased significantly in model group, the protein expression of Smad7 were also slowed in model group, the level of MDA was increased in model group, the contents of TGF-β1, TNF-α and the protein expression of Smad2 were all increased in model group（P〈0.01）. Compared with the model group, the EIP, EEP, RT, TV, EV, MV, AV, EF50 levels and the SOD activity were increased significantly in all groups of Xiefei Decoction. Meatime, the protein expression of Smad7 were also improved all groups of Xiefei Decoction（P〈0.05, P〈0.01）. As well as, the EF50 levels were increased obviously in middle-dose, high-dose group of Xiefei Decoction, the levels of TE and PEP were both ascended obviously in high-dose group of Xiefei Decoction（P〈0.05, P〈0.01）. But, the level of MDA was lowed in all groups of Xiefei Decoction, the contents of TGF-β1, TNF-α and the protein expression of Smad2 were all decreased in middle-dose, high-dose group of Xiefei Decoction（P〈0.05, P〈0.01）. Conclusion： Xiefei Decoction could inhibit TGF-β1/Smads signal transduction pathway by down regulation of TGF-β1 and Smad2 and up regulation of Smad7 and exerts an effect on anti-pulmonary fibrosis.