细胞外囊泡治疗急性肾损伤临床前研究的Meta分析

Extracellular vesicles for acute kidney injury in preclinical research:a meta-analysis

目的:急性肾损伤是临床常见危重症之一,存活患者的肾脏远期预后不容乐观。文章系统评价细胞外囊泡对急性肾损伤动物模型的有效性,希望为临床试验提供启发。方法:检索PubMed、Embase、Web of Science、Cochrane Library、万方、维普、中国知网和中国生物医学文献数据库中有关细胞外囊泡治疗急性肾损伤临床前研究的相关文章,检索时间为各数据库建立至2022-08-01,由2名研究人员独立提取数据,对文献采用SYRCLE动物实验偏倚风险评估表进行质量评价。采用RevMan 5.4和Stata 14.0软件对血肌酐、尿素氮、肿瘤坏死因子α、肾小管管状坏死与肾小管管型等结局指标进行Meta分析。结果:(1)共纳入19篇随机对照动物实验,包括399只啮齿动物,其中细胞外囊泡治疗组啮齿动物169只,对照组啮齿动物168只,干细胞治疗组啮齿动物62只。(2)Meta分析结果显示:与动物模型对照组相比,细胞外囊泡组血肌酐水平(SMD=-5.41,95%CI:-6.95至-3.88,P<0.001)、尿素氮水平(SMD=-4.57,95%CI:-5.94至-3.20,P<0.001)、肿瘤坏死因子α水平(SMD=-2.15,95%CI:-2.63至-1.68,P<0.001)明显降低,肾小管管状坏死(SMD=-6.15,95%CI:-9.66至-2.64,P=0.001)与肾小管管型(SMD=-3.33,95%CI:-4.17至-2.49,P=0.001)明显减少;细胞外囊泡组与间充质干细胞治疗组在改善血肌酐(SMD=-1.23,95%CI:-2.80-0.35,P=0.127)及尿素氮(SMD=-0.34,95%CI:-2.19-1.50,P=0.715)水平方面无显著差异。结论:细胞外囊泡有助于改善急性肾损伤动物模型的血肌酐和尿素氮水平,可显著降低肿瘤坏死因子α水平,并且减少肾小管管状坏死与肾小管管型,这些基础研究证据为下一步开展临床试验提供重要参考。

OBJECTIVE:Acute renal injury is one of the common clinical critical diseases,and the long-term prognosis of surviving patients is not optimistic.This study systemically assessed the effectivity of extracellular vesicles on animal models of acute kidney injury,hoping to inspire for clinical trials.METHODS:Articles related to the treatment of extracellular vesicles for acute kidney injury in preclinical animal models were retrieved from PubMed,Embase,Web of Science,Cochrane Library,WanFang,VIP,CNKI,and Chinese Biomedical Literature Database.The retrieval time was from the establishment of the database to August 1,2022.Data were independently extracted by two researchers.SYRCLE Animal Experiment Bias Risk Assessment table was used to evaluate the literature quality.RevMan 5.4 software and Stata 14.0 software were used to perform meta-analysis on serum creatinine,urea nitrogen,tumor necrosis factor-α,tubular necrosis and tubular type outcome indicators.RESULTS:(1)A total of 19 randomized controlled animal experimental studies were included,with 399 rodents.There were 169 rodents in the extracellular vesicle treatment group,168 rodents in the control group and 62 rodents in the stem cell treatment group.(2)The meta-analysis results demonstrated that serum creatinine level(SMD=-5.41,95%CI:-6.95 to-3.88,P<0.001)and urea nitrogen level(SMD=-4.57,95%CI:-5.94 to-3.20,P<0.001),and tumor necrosis factor-αlevel(SMD=-2.15,95%CI:-2.63 to-1.68,P<0.001)were significantly lower in the extracellular vesicle groups compared with the animal model control groups.Tubular necrosis(SMD=-6.15,95%CI:-9.66 to-2.64,P=0.001)and casts(SMD=-3.33,95%CI:-4.17 to-2.49,P=0.001)were significantly reduced.There was no significant difference in the improvement of serum creatinine between the extracellular vesicle group and the mesenchymal stem cell group(SMD=-1.23,95%CI:-2.80-0.35,P=0.127)and in the improvement of urea nitrogen(SMD=-0.34,95%CI:-2.19-1.50,P=0.715).CONCLUSION:Extracellular vesicles could improve the levels of serum creatinine and urea nitrogen in animal models with acute kidney injury,which could significantly reduce the level of tumor necrosis factor-α,tubular necrosis and casts.Extracellular vesicles for acute kidney injury provide an important reference for further clinical trials.