标题：TGF-β1/Smad通路在养肺保元汤治疗慢性阻塞性肺病合并肺间质纤维化中的作用

      作者：吴俣，刘良丽，朱晓龙    贵州中医药大学第一附属医院呼吸内科，贵州 贵阳 550000

      卷次： 2021年32卷2期

      【摘要】 目的 研究养肺保元汤治疗慢性阻塞性肺病(COPD)合并肺间质纤维化(PIF)中转化生长因子-β1(TGF-β1)/Smad通路的作用机制。方法 15只SD大鼠随机分为正常组(n=3)、模型组(n=4)、DcR3抗体组(n=4)和养肺保元汤组(n=4)。除正常组外，其他12只大鼠在烟熏箱内每天被动吸烟1 h，持续42 d，得到COPD合并PIF造模大鼠。造模结束后开始给药，DcR3抗体给药组大鼠尾静脉注射DcR3抗体，养肺保元汤给药组大鼠灌胃养肺保元汤，而模型组大鼠灌胃生理盐水，持续一个月。每周测量大鼠体质量。给药结束后处死大鼠，取大鼠血液，ELISA检测血清中 TGF-β1的含量；取大鼠肺部组织，采用HE染色观察组织纤维化程度，Tunnel染色观察肺上皮细胞凋亡情况，WB检测Smad2/3、Smad7蛋白的表达情况。结果 模型组大鼠体质量增长，大鼠肺泡变小，肺泡间质增厚有炎性细胞浸润，组织中有更多细胞凋亡；DcR3抗体给药组或者养肺保元汤给药组大鼠肺泡间质增生程度低于模型组，细胞凋亡水平也低于模型组；ELISA检测结果显示，各组大鼠血液中TGF-β1含量比较差异无统计学意义(P>0.05)；与正常组比较，模型组大鼠肺组织中Smad2、Smad3和Smad7蛋白质表达均明显上升，差异均有统计学意义(P<0.05)；与模型组比较，养肺保元汤组以及DcR3抗体组大鼠肺组织中Smad2、Smad3和Smad7蛋白质表达明显下降，差异均有统计学意义(P<0.05)；与养肺保元汤组比较，DcR3抗体组Smad3表达较高，Smad7表达量较低，差异均有统计学意义(P<0.05)，但Smad2表达量比较差异无统计学意义(P>0.05)。结论 养肺保元汤可能通过抑制肺组织中TGF-β1/Smad通路的活性达到减轻 COPD合并 PIF症状的效果。
      【关键词】 养肺保元汤；慢性阻塞性肺病；肺间质纤维化；转化生长因子-β/Smad；DcR3
      【中图分类号】 R563 【文献标识码】 A 【文章编号】 1003—6350（2021）02—0137—04

Role of TGF-β1/Smad pathway in the treatment of COPD complicated with pulmonary interstitial fibrosis treatedby Yangfei Baoyuan Decoction.
WU Yu, LIU Liang-li, ZHU Xiao-long. Department of Respiratory Medicine, the FirstAffiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550000, Guizhou, CHINA
【Abstract】 Objective To study the role of TGF-beta 1/Smad pathway in the treatment of chronic obstructivepulmonary disease complicated with PIF treated by Yangfei Baoyuan Decoction. Methods Fifty rats were divided intonormal group (n=3), model group (n=4), DcR3 antibody group (n=4), and Yangfei Baoyuan Decoction group (n=4). Ex-cept the normal group, rats were exposed in passive smoking for 1 hour a day in the fumigation box for 42 days, andCOPD with PIF model rats were obtained. The rats in the DcR3 antibody group were injected with DcR3 antibody in thetail vein, and the rats in the Yangfeibaoyuan Decoction group were given Yangfeibaoyuan Decoction in the stomach, whilethe rats in the model group were given saline in the stomach for one month. The weight of rats was measured weekly. Afteradministration, rats were executed, blood samples were taken and serum TGF-beta 1 was detected by ELISA; lung tissueswere taken for detection: HE staining was used to observe the degree of fibrosis, Tunnel staining was applied to observethe apoptosis of pulmonary epithelial cells, and WB was used to detect the expression of Smad2/3 and Smad7 protein.Results In the model group, the weight gain of rats decreased, alveoli became smaller, alveolar interstice was thickeningwith inflammatory cell infiltration, and there were more apoptotic cells in tissues. In DcR3 antibody group or YangfeiBaoyuan Decoction group, the degree of alveolar interstitial hyperplasia and apoptosis were lower than those in modelgroup. ELISA results showed that there was no significant difference in the content of TGF-β1 in the blood of rats in eachgroup (P>0.05). Compared with the normal group, the protein expression of Smad2, Smad3, and Smad7 in the lung tissueof model group was significantly increased (P<0.05). Compared with the model group, the protein expression of Smad2,Smad3, and Smad7 in lung tissue of rats in Yangfei Baoyuan Decoction group and DcR3 antibody group was significantlydecreased (P<0.05). Compared with the Yangfei Baoyuan Decoction group, the protein expression of Smad3 in the lungtissue of rats in the DcR3 antibody group were significantly higher (P<0.05), the expression of Smad7 was significantlylower (P<0.05), and the expression of Smad2 was not significantly different (P>0.05). Conclusion Yangfei Baoyuan De-coction treatment attenuated the symptoms of COPD with PIF by inhibiting TGF-beta 1/Smad pathway in lung tissue.
      【Key words】 Yangfei Baoyuan Decoction; Chronic obstructive pulmonary disease; Pulmonary interstitial fibro-sis; TGF-β1/Smad; DcR3