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3讨论
我们的研究结果显示，H2O2在1nmol/L ～10μmol/L的可促进晶状体上皮细胞增殖，而在100μmol/L～1mmol/L则抑制细胞增生；在1nmol/L～10μmol/L H2O2能刺激晶状体上皮细胞产生VEGF，在10nmol/L和10μmol/L时VEGF的量最高，而在100μmol/L和1mmol/L时无VEGF产生。提示低剂量的H2O2刺激晶状体上皮细胞产生VEGF，同时促进培养的晶状体上皮细胞增生。
H2O2对晶状体上皮细胞的增殖活力有明显的影响。低浓度的 H2O2刺激可促进晶状体上皮细胞增殖，且以10nmol/L刺激增生效应最显著。而高浓度的H2O2可以导致细胞毒性，引起细胞死亡，这与以往的研究结果相似[11]。尚不致细胞毒性浓度的H2O2是一种信号转导分子[12]。H2O2可能通过其信号分子作用，向细胞传达某种促增殖信号，促进晶状体上皮细胞增殖。研究发现，H2O2可促进生长因子受体的磷酸化[13],推测H2O2可能会引起晶状体上皮细胞分泌某些生长因子，从而促进细胞增殖。已有研究报道低剂量的H2O2刺激晶状体上皮细胞产生CTGF[3]和LEDGF[4]，但对它们所引起的细胞生物学效应尚未见进一步报道。关于VEGF，有研究显示在缺氧条件下，小鼠晶状体上皮内VEGF的表达增高[14]，尚没有H2O2对晶状体上皮细胞VEGF表达影响的报告。我们的研究显示，低剂量H2O2不仅能可刺激晶状体上皮细胞产生VEGF，而且在相近的H2O2剂量范围内也刺激晶状体上皮细胞增生，提示低剂量H2O2可能通过刺激VEGF分泌引起细胞增殖。
本研究显示高浓度的H2O2使细胞的增殖能力下降，与此对应的H2O2没有刺激VEGF的高表达，表现出高浓度H2O2对细胞的毒性作用。
已有研究发现VEGF可上调脐静脉内皮细胞表达谷胱甘肽及谷胱甘肽过氧化物酶从而增加脐静脉内皮细胞的抗氧化能力[15]；VEGF可促进Ｍüller细胞增殖，对其有保护作用[16,17]；在晶状体上皮细胞VEGF可引起ERK的磷酸化水平增加[18]。我们推测VEGF可能通过ERK介导的信号转导途径影响细胞增殖能力和抗氧化能力。
氧化应激在白内障的形成起着重要作用，本研究结果提示氧化应激可能通过诱导晶状体上皮细胞产生VEGF而引起晶状体上皮细胞的功能变化，这对探讨白内障的发生机理可能是一个新的切入点。
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