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    柴婧, 王榆元, 张静怡, 牛强, 胡云华, 李毓, 王海霞, 李述刚. 砷对PI3K/AKT信号通路调节效应的Meta分析[J]. 环境卫生学杂志, 2020, 10(1): 31-37. DOI: 10.13421/j.cnki.hjwsxzz.2020.01.006
    引用本文: 柴婧, 王榆元, 张静怡, 牛强, 胡云华, 李毓, 王海霞, 李述刚. 砷对PI3K/AKT信号通路调节效应的Meta分析[J]. 环境卫生学杂志, 2020, 10(1): 31-37. DOI: 10.13421/j.cnki.hjwsxzz.2020.01.006
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    CHAI Jing, WANG Yuyuan, ZHANG Jingyi, NIU Qiang, HU Yunhua, LI Yu, WANG Haixia, LI Shugang. Meta-analysis of Multiple Regulatory Effects of Arsenic on PI3K/AKT Signaling Pathway[J]. Journal of Environmental Hygiene, 2020, 10(1): 31-37. DOI: 10.13421/j.cnki.hjwsxzz.2020.01.006
    Citation: CHAI Jing, WANG Yuyuan, ZHANG Jingyi, NIU Qiang, HU Yunhua, LI Yu, WANG Haixia, LI Shugang. Meta-analysis of Multiple Regulatory Effects of Arsenic on PI3K/AKT Signaling Pathway[J]. Journal of Environmental Hygiene, 2020, 10(1): 31-37. DOI: 10.13421/j.cnki.hjwsxzz.2020.01.006
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    砷对PI3K/AKT信号通路调节效应的Meta分析

    Meta-analysis of Multiple Regulatory Effects of Arsenic on PI3K/AKT Signaling Pathway

      摘要
    • 摘要:
      目的 系统评价砷（arsenic，As）对PI3K/AKT信号通路的多种调节效应，为揭示砷毒性作用机制提供理论依据。
      方法 2名研究者独立地评价中国知网、维普、万方、Cochrane、Embase、PubMed、Web of Science等数据库的文献质量，提取资料并进行交叉核对。对纳入的研究结果采用RevMan 5.3和Stata 12.0进行Meta分析。
      结果 在体外实验中，与对照组相比，砷干预组PI3K、P-AKT水平均低于对照组，PTEN水平高于对照组，差异有统计学意义（Z分别为3.01、3.15和1.97，P < 0.05）；亚组分析发现，长时间（>24 h）砷干预组PTEN水平高于对照组，PI3K和P-AKT（ser473）水平均低于对照组，短时间（≤ 24 h）砷干预组P-AKT水平低于对照组，差异有统计学意义（Z分别为2.06、2.34、2.92和2.79，P < 0.05）。高浓度（≥ 3 μmol/L）砷干预组PI3K及P-AKT水平均低于对照组，差异有统计学意义（Z分别为2.46和3.34，P < 0.05）。砷与PI3K抑制剂联合处理后的AKT、P-AKT及P-AKT（ser473）的表达比砷干预组下降更为明显。在体内实验中，砷干预组PI3K、P-AKT水平均低于对照组，差异有统计学意义（Z分别为2.40、4.25，P < 0.05）；亚组分析可见，长时间（>14 d）砷干预组P-AKT水平，短时间（≤ 14 d）砷干预组PI3K、P-AKT、AKT水平均低于对照组，差异有统计学意义（Z分别为3.01、4.04、3.67和2.17，P < 0.05）。高浓度（>3 mg/kg）砷干预组PI3K、P-AKT，低浓度（≤ 3 mg/kg）砷干预组AKT、P-AKT水平均低于对照组，差异有统计学意义（Z分别为4.04、3.00、4.33和2.35，P < 0.05）。凋亡指标分析显示，砷干预后，凋亡相关蛋白Bax、Cytochrome C、Caspase3、Caspase9、PARP和Apoptosis rate表达水平较对照组均增加，差异有统计学意义（Z分别为3.34、2.47、2.05、2.36、2.21和3.16，P < 0.05），Bcl-2蛋白表达水平与对照组相比下降（Z=2.05，P < 0.05）。
      结论 砷可以通过抑制PI3K/AKT信号通路诱导细胞的调亡，其作用受到剂量、作用时间的影响。

       

      Abstract:
      Objective To evaluate systematically various regulating effects of arsenic on the PI3K/AKT signaling pathway, providing a basis for revealing the mechanism of arsenic toxicity.
      Methods Two researchers independently evaluated the literature quality of databases, such as the China National Knowledge Infrastructure, Vip, Wanfang, Cochrane, Embase, PubMed and Web of Science. They extracted and cross-checked the data. The included result were meta-analyzed using RevMan 5.3 and Stata 12.0.
      Results In vitro experiments, the levels of PI3K and P-AKT in the arsenic intervention group were significantly lower than those in the control group, and the levels of PTEN were significantly higher than those in the control group (Z values were 3.01, 3.15, and 1.97, respectively, P < 0.05). Subgroup analysis found that the PTEN level in the arsenic intervention group was significantly higher than that in the control group, and the levels of PI3K and P-AKT (ser473) were significantly lower than those in the control group (Z values were 2.06, 2.34, and 2.92 respectively, P < 0.05). P-AKT level in the short-term (≤ 24 h) arsenic intervention group was significantly lower than that in the control group (Z=2.79, P < 0.05). Levels of PI3K and P-AKT in the high-concentration (≥ 3 μmol/L) arsenic intervention group were significantly lower than those in the control group (Z values were 2.46 and 3.34, respectively, P < 0.05).The expressions of AKT, P-AKT and P-AKT (ser473) after arsenic combined with PI3K inhibitors significantly decreased than the arsenic intervention group. In vivo experiments, the levels of PI3K and P-AKT in the arsenic intervention group were significantly lower than those in the control group (Z values were 2.40 and 4.25 respectively, P < 0.05). Subgroup analysis showed that the P-AKT level of the arsenic intervention group was significantly lower than that of the control group for a long time (>14 d) (Z=3.01, P < 0.05). Short-term (≤ 14 d) arsenic intervention group of PI3K, P-AKT, AKT levels were significantly lower than those in the control group (Z values were 4.04, 3.67, and 2.17, respectively, P < 0.05). Levels of PI3K and P-AKT in the high-concentration (>3 mg/kg) arsenic intervention group and the levels of AKT and P-AKT in the low-concentration (≤ 3 mg/kg) arsenic intervention group were significantly lower than those in the control group (Z values were 4.04, 3.00, 4.33, and 2.35, respectively, P < 0.05). Analysis of apoptosis indicators showed that after arsenic intervention, the expression levels of apoptosis-related proteins Bax, Cytochrome C, Caspase3, Caspase9, PARP, and apoptosis rate all significantly increased compared with the control group (Z were 3.34, 2.47, 2.05, 2.36, 2.21 and 3.16 respectively, P < 0.05), while Bcl-2 protein expression level significantly decreased (Z=2.05, P < 0.05).
      Conclusions Arsenic can induce cell apoptosis by inhibiting PI3K/AKT signaling pathway, and its effect is affected by dose and time of action.

       

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