丹红注射液治疗特发性肺纤维化临床疗效及安全性的Meta分析

辛丽丽+姜淼+张赓+龚婕宁

[摘要]计算机检索 Pubmed，EMbase，Web of Science，Cochrane Library，CNKI，CBM，万方数据库，VIP，检索时限均从建库至2016年5月，同时补充互联网及手检相关杂志的文献，纳入有关丹红注射液治疗特发性肺纤维化的随机对照试验（RCT）和半随机对照试验（quasi-RCT），并追溯纳入文献的参考文献。由2名研究者按纳入与排除标准独立筛选文献、提取资料并评价质量后，使用RevMan 5.3进行Meta分析，系统评价丹红注射液治疗特发性肺纤维化的疗效和安全性。共纳入12个RCT，包括844例患者，试验组423例，对照组421例。Meta分析结果显示：与对照组比较，丹红注射液组对临床有效率[RR=1.36，95%CI（1.25，1.49），P<0.000 01]， DLCO提高值[MD=4.25，95%CI（3.32，5.18），P<0.000 01]， PaO2提高值[MD=14.51，95%CI（12.35，16.68），P<0.000 01]的改善作用更显著，差异具有统计学意义。描述性分析结果显示丹红注射液能显著降低血清TGF-β1含量。试验组不良反应症状较轻、发生率低，提示丹红注射液治疗特发性肺纤维化的近期安全性较高，耐受性良好。现有证据表明，短期内（<12周）使用丹红注射液可改善特发性肺纤维化患者的临床情况、提高DLCO及PaO2、降低血清TGF-β1含量，且不良反应少，安全性较高。但由于纳入研究的局限性，急需高质量RCT更深入更全面地探究丹红注射液对特发性肺纤维化的短期及长期有效性及安全性。

[关键词]丹红注射液； 特发性肺纤维化； 系统评价； Meta分析； 随机对照试验

[Abstract]To systematically review the efficacy and safety of Danhong injection for patients with idiopathic pulmonary fibrosis（IPF）， two researchers electronically searched PubMed， EMbase， Web of Science， Cochrane Library， CNKI， CBM， WanFang Data and VIP databases from the date of establishment to May 2016 for all randomized controlled trials（RCTs） and quasi-RCTs on the use of Danhong injection in patients with IPF. Manual search in relevant journals and search of relevant literature on other websites were also performed. The data extraction and quality assessment of included RCTs and quasi-RCT were conducted by two reviewers independently. Then， Meta-analysis was conducted by using RevMan 5.3 software. A total of 12 RCTs involving 844 patients were included， 423 cases in experiment group and 421 cases in control group. The results of meta-analysis indicated that the Danhong injection group was superior than the control group in clinical effectiveness（RR=1.36， 95%CI 1.25 to 1.49， P<0.000 01）， increased DLCO value（MD=4.25， 95%CI 3.32 to 5.18， P<0.000 01）， and increased PaO2 value（MD=14.51， 95%CI 12.35 to 16.68， P<0.000 01）. The analysis results showed that Danhong injection could significantly reduce the level of TGF-β1 in serum. There were no serious or frequently happened adverse effects in the Danhong injection group， indicating high safety and good tolerance of Danhong injection in treatment of IPF. The current evidences suggested that Danhong injection in short term use（<12 weeks） could increase clinical effectiveness， improve DLCO and PaO2， and decrease the level of TGF-β1 in serum of IPF patients， with less adverse effects. However， these results should be carefully interpreted due to the low methodology quality and small sample size of trials， and this conclusion had to be further verified by high quality， large scale and double blinded RCTs.

[Key words]Danhong injection； idiopathic pulmonary fibrosis； systematic review； Meta-analysis； randomized controlled trial

doi：10.4268/cjcmm20162024

特发性肺纤维化（idiopathic pulmonary fibrosis，IPF）是机体对各种原因引起的肺泡损害的一种应答反应，病理过程包括上皮细胞的内部损伤、炎性渗出、肌成纤维细胞形成、成纤维细胞聚集、纤维化瘢痕形成等一系列过程，导致肺部组织结构发生不可逆性的病理变化，肺部无法进行正常血气交换，最终导致患者呼吸衰竭而死亡，是多种肺部疾病的共同结局。由于对IPF发病机制的理解仍处于多种有研究观察结果的“拼图”时代，其形成过程的复杂性决定了单一特异性靶向药物疗效的不确切性。

中医古文献无“肺纤维化”病名记载，根据临床表现的相似性，本病多属于“肺痿”、“肺痹”、“喘证”、“咳嗽”、“肺胀”等范畴。中医学认为肺纤维化病变的实质是“血络瘀滞”，多由温病肺热证及慢性肺系疾病反复感染后发展而来。丹红注射液是丹参和红花提取纯化制成的复方制剂，丹参、红花均有活血化瘀之用，在此作用的基础上，在中医理论的指导下，广泛应用于临床心脑血管、内分泌、呼吸、消化等各种疾病的治疗。……