砷与p38 MAPK信号通路研究的系统评价及Meta分析

Systematic evaluation of arsenic and p38 MAPK signaling pathway

目的本研究通过Meta分析旨在探讨MAPK信号通路中p38通路在砷诱导细胞调亡过程中的作用,为研究砷毒作用机制以及砷中毒的防治提供参考。方法在PubMed、Web of Science、ScienceDirect、Cochrane library、CNKI、WanFang、VIP、SinoMed等数据库中全面检索文献,采用ToxRTool进行文献质量评价,以细胞凋亡率、细胞存活率、p-p38表达量为干预组的结局指标,采用ReviewManage5.3对数据进行统计学分析,以Q检验和I 2统计量法进行异质性检验和敏感性分析,用漏斗图来判断发表偏倚。结果最终纳入文献13篇。与对照组相比,砷干预组细胞凋亡率MD为31.10,95%CI(10.14,52.05)高于对照组,Z=2.91,P<0.05,两组间差异有统计学意义;砷干预组细胞存活率P<0.0001,I 2>50%,按照剂量和时间进行亚组分析,探讨异质性来源,结果两种因素的异质性I 2均无统计学意义(P>0.05),显示两种因素均不是异质性来源;p-p38表达量的假设检验结果为Z=1.81,P=0.07,两组间差异有统计学意义。结论砷及其化合物能诱导细胞凋亡;砷诱导细胞凋亡的机制可能与激活p38,增加p-p38蛋白表达水平有关。

Objective To investigate the role of p38 pathway in arsenic-induced cell apoptosis in MAPK signaling pathway by Meta analysis.It provides a reference for studying the mechanism of arsenic toxicity and the prevention and treatment of arsenic poisoning.Methods To search the literature in Pubmed,Web of Science,ScienceDirect,Cochrane library,CNKI,WanFang,Vip and SinoMed.ToxRTool was used to evaluate the quality of the literature.The results of apoptosis rate,cell survival rate and p-p38 expression were analyzed by ReviewManage 5.3.Heterogeneity test and sensitivity analysis were performed by Q test and I 2 statistical method,and the publication bias was judged by funnel plot.Results Finally,13 articles were included in the literature.Compared with the control group,the apoptosis rate of the arsenic intervention group was 31.10,95%CI(10.14,52.05)was higher than that of the control group,Z=2.91,P<0.05.And the difference between the two groups was statistically significant.The survival rate of arsenic intervention group(P<0.0001,I 2>50%)was highly heterogeneous.So the heterogeneity sources were investigated by subgroup analysis according to dose and time.There was no significant change in heterogeneity I 2 between the dose and time.The hypothesis test results of p-p38 expression were Z=1.81,P=0.07,and the difference between the two groups was statistically significant.Conclusion Arsenic and its compounds can induce apoptosis.The mechanism of arsenic-induced apoptosis may be related to activating p38 and increasing the expression level of p-p38 protein.