补阳还五汤治疗气虚血瘀证型结缔组织病相关性肺纤维化的临床疗效  

Clinical Trial of Buyang Huanwutang in Treatment of Connective Tissue Disease-associated Pulmonary Fibrosis with Syndrome of Qi Deficiency and Blood Stasis

作　　者：蒋桓宇 杨晗[1] 代倩 吴新辉 汤吴以诺 王飞[1] 杜全宇 JIANG Huanyu;YANG Han;DAI Qian;WU Xinhui;TANGWU Yinuo;WANG Fei;DU Quanyu(Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610075 China)

机构地区：[1]成都中医药大学附属医院,成都610075

出　　处：《中国实验方剂学杂志》2022年第21期104-112,共9页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金面上项目(82174347);国家自然科学基金青年基金项目(82104829);四川省中医药管理局科学技术研究专项(2020JC0049)。

摘　　要：目的:明确补阳还五汤对结缔组织病相关性肺纤维化(CTD-ILD)气虚血瘀证的疗效和安全性,并对补阳还五汤可能的抗纤维化作用机制进行探索。方法:采用随机对照单盲的研究方法,将66名患者分为观察组和对照组,观察组接受补阳还五汤联合一般常规治疗,对照组接受一般常规治疗,治疗周期为4周。主要疗效指标为干预结束后用力肺活量(FVC)较基线的改变值,次要疗效指标包括用力肺活量占预计值百分比(FVC%pred)、第1秒用力呼气容积占预计值百分比(FEV1%pred)、King间质性肺疾病简短量表(K-BILD)问卷、6分钟步行距离(6MWD)、羟脯氨酸(HYP)、基质金属蛋白酶(MMP)、金属蛋白酶组织抑制因子-1(TIMP-1)、转化生长因子-β(TGF-β)较基线的改变值。符合方案的患者纳入主要分析,对缺失数据进行多重插补后进行敏感性分析,安全性采用安全性分析集。结果:66例受试者(纳入敏感性分析)中34例进入观察组,32例进入对照组,最终接受全程试验干预的患者有60例(纳入主要分析)。干预结束后观察组FVC较基线增加,对照组较基线降低,组间差异有统计学意义(P<0.01),敏感性分析和主要分析的结果一致;观察组FVC%pred、FEV1%pred、6MWD、K-BILD总分较基线的改变值均优于对照组(P<0.01),敏感性分析和主要分析的结果一致。观察组TIMP-1较治疗前显著下降(P<0.05),但两组TIMP-1较基线改变值无统计学意义,观察组HYP、MMP-9、TGF-β较基线下降多于对照组(P<0.05)。两组用药期间常见不良反应为咳嗽、腹泻、恶心、皮疹、上消化道感染,两组不良反应事件的发生率差异无统计学意义。结论:补阳还五汤可以改善CTD-ILD患者肺功能、运动功能和生活质量,且具有较好的安全性;其机制可能和降低TGF-β、MMP-9、TIMP-1水平,维持MMP-9/TIMP-1平衡有关。Objective:To evaluate the effect and safety of Buyang Huanwutang in treatment of connective tissue disease-associated pulmonary fibrosis in the patients with syndrome of Qi deficiency and blood stasis and explore the possible anti-fibrosis mechanism of Buyang Huanwutang.Method:Sixty-six patients with connective tissue disease-associated pulmonary fibrosis with syndrome of Qi deficiency and blood stasis were randomized to receive either Buyang Huanwutang combined with routine therapy or routine therapy for 4 weeks.The primary outcome indicator was change in forced vital capacity(FVC)from the baseline,and the secondary outcome indicators included the changes in percentage of predicted forced vital capacity(FVC%pred),percentage of forced expiratory volume in first second to predicted value(FEV1%pred),King’s Brief Interstitial Lung Disease(K-BILD)total score,6 minute walking distance(6MWD),hydroxyproline(HYP),matrix metalloproteinase(MMP),tissue inhibitor of metalloproteinase-1(TIMP-1),and transforming growth factor-β(TGF-β)from baseline.Patients in line with the inclusion criteria were included in the primary analysis,and sensitivity analysis was performed after multiple imputation of missing data.Safety set was adopted for safety analysis.Result:The 66 patients(included in the sensitivity analysis)meeting the inclusion criteria included 34in the observation group and 32 in the control group,and 60 patients finally received the whole trial intervention(included for primary analysis).Compared with the baseline,the FVC increased in the observation group and decreased in the control group after intervention(P<0.01),which was consistent between the sensitivity analysis and the primary analysis.The changes in FVC%pred,FEV1%pred,6MWD,and K-BILD total score from baseline in the observation group were superior to those in the control group(P<0.01),with consistent results between the sensitivity analysis and the primary analysis.TIMP-1 in the observation group decreased compared with baseline(P<0.05),while TIMP-1 in the

关 键 词：补阳还五汤 结缔组织病相关性肺纤维化(CTD-ILD) 气虚血瘀证 疗效性 安全性 

分 类 号：R242[医药卫生—中医临床基础] R2-031[医药卫生—中医学] R287R593.2R256.1