灯盏花素注射剂治疗糖尿病性肾病的有效性和安全性:随机对照试验的系统评价和Meta分析

Efficacy and safety of Breviscapine Injection in treatment of diabetic nephropathy: systematic review and Meta-analysis of randomized controlled trials

系统评价灯盏花素注射剂治疗糖尿病性肾病的有效性和安全性。全面检索国内外八大电子数据库及临床试验注册库,搜集关于灯盏花素注射剂(以下简称"灯盏花素")治疗糖尿病性肾病(diabetic nephropathy,DN)的随机对照试验。根据Cochrane系统评价标准进行资料筛选、提取和质量评价。对最终纳入的文献采用Rev Man5. 3软件进行Meta分析或仅做描述性分析。本研究共纳入29篇文献,包含37个研究,涉及2 097例患者,试验组为1 054例,对照组为1 043例。所纳入的临床研究总体质量偏低。Meta分析显示:①在DNⅢ期中,常规治疗+灯盏花素在总有效率,24 h UTP,SCR,BUN,UEAR,ALB,m ALB方面优于常规治疗(RR总有效率=1. 60,95%CI[1. 32,1. 93],P<0. 000 01; SMD24 h UTP=-1. 21,95%CI[-1. 56,-0. 87],P<0. 000 01; MDSCR=-6. 33,95%CI[-9. 20,-3. 46],P<0. 000 1; MDBUN=-6. 6,95%CI[-1. 10,-0. 22],P=0. 003; MDUEAR=-20. 30,95%CI[-28. 14,-12. 46],P <0. 000 01; MDALB=0. 47,95%CI[0. 42,0. 52],P <0. 000 01; MDmALB=-10. 03,95%CI[-10. 62,-9. 46],P<0. 000 01)。②在DNⅣ期中,常规治疗+灯盏花素在总有效率(1个研究),24 h UTP,SCR,BUN方面优于常规治疗(RR总有效率=1. 57,95%CI[1. 10,2. 25],P=0. 01; SMD24 h UTP=-0. 52,95%CI[-0. 71,-0. 33],P <0. 000 01;MDSCR=-35. 38,95%CI[-48. 57,-22. 19],P<0. 000 01; MDBUN=-1. 89,95%CI[-3. 01,-0. 77],P<0. 000 01)。③在DNⅤ期中,常规治疗+灯盏花素在SCR方面优于常规治疗(MD=-26. 35,95%CI[-47. 45,-5. 24],P=0. 01),而在24 h UTP,BUN,ALB方面与常规治疗对比无统计学差异。④目前无法从现有证据中获得灯盏花素注射剂治疗该病所发生的不良反应具体判断信息。基于现有证据,灯盏花素注射剂联合常规治疗治疗糖尿病性肾病有一定的疗效,特别是DNⅢ,Ⅳ期的研究较多,所改善的结局指标有较明显的疗效优势,而该药的安全性尚需进一步探讨。由于纳入研究质量普遍偏低,影响结果的精确性,尚需更多设计严紧、高质量、多中心随机双盲对照试验为临床实践提供证据支撑。

This study aimed to systematically evaluate the efficacy and safety of Breviscapine Injection in the treatment of diabetic nephropathy (DN). Eight electronic databases and ClinicalTrials.gov were searched to collect randomized controlled trials on Breviscap-ine Injection in the treatment of DN. According to the Cochrane Handbook 5. 1, two independent reviewers screened out the literatures, extracted data and assessed the quality of the studies included. RevMan5. 3 software was used for the data analysis. A total of 29 studies containing 37 trials were included, involving 2 097 patients, 1054 cases in test groups and 1043 cases in control groups. The clinical studies included had a low overall quality. According to Meta-analysis:①Conventional therapy plus breviscapine injection was superior to conventional therapy in total efficiency rate, 24 h UTP, SCR, BUN, UEAR, ALB and mA LB during DN stage Ⅲ(RR lota) effectiVe rate - 1.60, 95%CI [ 1. 32, 1.93], P<0.00001;SMD24h UTP =-1. 21, 95%C1[-1.56,-0.87], P<0.00001;MDSCR =-6. 33, 95%CI[- 9.20,-3. 46], P<0.0001;MDBUN =-6. 6, 95%CI[-1. 10,-0. 22], P=0. 003;MDUEAR =-20. 30, 95%CI [-28. 14,-12. 46],P< 0.00001;MDalb=0.47, 95%CI[0. 42, 0.52], P<0.00001;MDmALB =-10. 03, 95%CI[-10. 62,-9. 46], P<0.00001).②Conventional therapy plus Breviscapine Injection was better than conventional therapy in total efficiency rate ( only 1 study), 24 h UTP, SCR and BUN during DN stageⅣ(RRtotal dffective rate-1.57,95%CI[1. 10, 2.25], P二0.01;SMD24hUTP =-0. 52, 95%CI [-0.71,-0. 33], P<0.00001;MDSCR =-35. 38, 95%CI[-48. 57,-22. 19], P<0.00 01;MDBL1N =-1. 89, 95%CI [-3.01,-0. 77], P< 0.00001).③Conventional therapy plus Breviscapine Injection was better than conventional therapy in SCR ( MD =-26. 35, 95%CI [-47. 45,-5. 24], P =0.01), but with no significant difference in 24 h UTP, BUN and ALB during DN stage V.④It was impossible to obtain the specific judgment information on the adverse reactions of Breviscapine Injection in the treatment of the disease from the existing evidences. The current evidences suggest that the combination of Breviscapine Injection and conventional therapy had a certain curative effect in the treatment of DN, especially in stages Ⅲ and Ⅳ. The safety of Breviscapine Injection needs to be further explored. Because the low quality of the study impacted the accuracy of the result, more rigorous, high-quality, multi-center, randomized doubleblind controlled trials are required to increase the support of the evidences in the future.