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2.5 HO1与糖尿病视网膜病变
糖尿病视网膜病变主要是视网膜微血管的损害，随后引起视网膜一系列的病理改变。糖尿病的糖代谢紊乱是产生糖尿病视网膜病变的主要原因。以往研究证明氧化应激也是糖尿病微血管病变的原因之一。在对糖尿病患者视网膜色素上皮细胞的研究中发现糖尿病患者视网膜色素上皮细胞HO1mRNA较正常人明显减少，因此推测糖尿病患者视网膜色素上皮细胞HO1表达减少促成视网膜易于受糖尿病代谢紊乱损害。在链脲酶素诱导的鼠糖尿病模型中，发现视网膜HO1mRNA和ET1mRNA增加，彩色多普勒分析视网膜抵抗力增加，而给予锌原卟啉Ⅸ（SnPPⅨ）和molsidomine（NO供体）治疗，ET1mRNA和iNOSmRNA增加，HO1 mRNA减少，视网膜抵抗力降低。说明在糖尿病早期，HO1表达增加，调节血管因子NO的表达，从而改善视网膜血管功能［18］。因此，进一步研究HO1与糖尿病视网膜微血管瘤的关系，或许可以成为临床上糖尿病视网膜病变治疗的又一可靠方法。 此外，研究还显示，新生儿出生时HO1mRNA和HO1蛋白表达比足月儿低，所以容易发生新生儿视网膜病变［19］。
3问题与展望
大多数研究已证实HO1系统在视网膜氧化应激损伤中发挥保护作用，为临床治疗视网膜光变性、AMD、缺血再灌注损伤、糖尿病视网膜疾病、毒性物质的视网膜损害等方面提供了新的治疗思路，但尚存在问题如下：(1)人HO1基因启动子多态性决定诱导HO1活性要遵循个体化原则；(2) 某些情况下过度表达HO1及其降解产物可能对机体带来不良影响。(3)尚无特异性诱导活性药物。目前发现，环核苷酸(cGMP)和心房利尿钠肽(atrial natriuretic peptide)类受体，可明显增加细胞内cGMP水平，它们可特异性诱导HOl在肝细胞和培养的内皮细胞上表达，并已显示具有保护内皮细胞对抗α肿瘤坏死因子介导的细胞毒性以及肝细胞对抗氧化应激引起的缺血再灌注损伤等作用。另一候选者则可能是前列腺素。前列腺素cyPGs可特异性诱导HOl在鼠神经元上表达，对免疫反应在神经疾病病理机制有治疗作用［20］。（4）现有HO1诱导药物大多具氧化毒性，可能对机体产生一定的不良反应；（5）基因疗法尚有一些不足，如何合理应用需进一步研究。
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