2.2.1 Ang/Tie信号传导系统在DM患者体内的表达变化在DR患者体内Ang/Tie信号传导系统的成员增加。糖尿病眼部重要的并发症是视网膜血管渗漏（血管渗漏是新生血管的标志）和毛细血管无灌注。DR后期一个重要的改变就是视网膜缺血、缺氧、诱导VEGF上调，刺激视网膜新生血管形成，这是缺血诱导血管渗漏的主要原因。

    Takagi等[16]研究显示：人视网膜血管增殖标本中， Ang-2，Tie-2表达均有升高；且在缺血性视网膜疾病所致的视网膜血管增殖膜中Ang-2，Tie-2表达明显高于非缺血性视网膜疾病。支持这一观点的另外一些实验是Chiarelli等[17]于2002年所做测定，他们测定了223个糖尿病（DM）患者的血清Ang（sAng）水平,发现DM儿童Ang血清浓度升高，微血管并发症与血浆Ang水平显著相关，长期严格控制血糖能使Ang浓度下降。Malamitsi- Puchner等[18]发现在胰岛素依赖性糖尿病（IDDM）中，sAng水平显著升高，女性的sAng水平高于男性。与此同时，Ozaki等[19]收集了30例PDR病例和21例增生性玻璃体视网膜病（proliferative vitreoretinopathy, PVR）患者的玻璃体液，经过检测发现Ang水平均有所升高。

    2.2.2 Ang-1对DR的保护作用  在人类和啮齿类动物DR早期就有部分白细胞通过细胞间黏附分子-1（ICAM-1）黏附于视网膜血管并且引致毛细血管阻塞，导致内皮细胞损伤和死亡以及血—视网膜屏障破坏[20,21]。Joussen等[15]发现Ang-1可以阻止和逆转糖尿病视网膜血管病变，在给予糖尿病大鼠模型球内注射不同剂量Ang-1后结果发现：Ang-1可以抑制血—视网膜屏障破坏，并呈剂量依赖性；Ang-1可以保护血管内皮细胞免受白细胞介导的内皮细胞损伤作用；Ang-1可以降低VEGF和ICAM的mRNA和蛋白水平，从而降低Akt激酶活性，降低视网膜内皮型一氧化氮合酶（eNOS）和一氧化氮（NO）水平；Ang-1也可以通过降低视网膜细胞外信号调节激酶（Erk激酶）活性，减少白细胞黏附血管内皮细胞，并抑制该激酶促内皮细胞死亡的作用。

    3 Ang在DR治疗中的展望

    DR早期病理改变为视网膜微血管通透性升高，DR发展到后期，将由NPDR期发展为以视网膜新生血管和纤维化为特征的PDR期，在PDR期视网膜新生血管引起的渗漏对患者的视力影响极大，如果能够有效的抑制视网膜新生血管引起的渗漏必将抑制DR的进一步发展。目前的研究表明，Ang-1具有调节内皮之间、内皮—基质之间相互作用, 促进血管成熟并维持血管结构，在VEGF等生长因子的存在下, 由于其抗凋亡、促内皮迁移的作用, 增强了VEGF的促内皮芽性生长及血管网络形成作用，而Ang-2做为Ang-1的拮抗剂能拮抗Ang-1的这些生物效应。如何在DR的状况下调整Ang/Tie-2信号传导系统各成员的表达及作用，使其在DR早期血管重建，血管稳定，防渗漏中最大程度的发挥有益作用，是一个极有研究价值值得深入研究的问题。

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