4 糖尿病性眼表改变发病机制及病理变化
4.1 蛋白非酶糖基化 Rehany等 [14] 应用透射电子显微镜观察发现,糖尿病动物模型小鼠角膜后弹力层胶原存在形态改变,亦发现糖尿病患者角膜上 皮细胞中存在糖原颗粒积聚,基质层和后弹力层中出现120nm宽的异常胶原纤维束分布,认为此改变可反映糖尿病患者机体内发生过度糖基化作用.Ishino等 [15] 报道,角膜自发荧光与糖尿病糖基化的终产物及吡啶核苷酸有关.
4.2 醛糖还原酶通路 据报道,应用醛糖还原酶抑制剂后糖尿病病人角膜内皮细胞形态的变异系数及六边形细胞比例显著优于未用药患者.在糖尿病小鼠发病中早期应用醛糖还原酶抑制剂亦可阻止角膜内皮细胞形态的变异及六边形细胞比例的减少.糖尿病角膜内皮细胞的形态学改变可能与细胞内山梨醇代谢途径有关,即在醛糖还原酶作用下,高浓度葡萄糖转化为山梨醇,而在细胞内山梨醇代谢缓慢,使山梨醇蓄积于细胞内,引起细胞内渗透压增高,导致细胞肿胀、胞膜破裂、微绒毛消失、细胞排列疏松、细胞形态改变及细胞核皱缩等一系列形态学改变.
4.3 蛋白激酶通道 血糖升高可激活蛋白激酶C,增加前列腺素、氧自由基及一氧化氮的产生,降低前列环素的产生,增强Na + -K + -ATP酶及Ca 2+ -ATP 酶的活性,引起细胞功能受损 [16] .
4.4 肌醇代谢异常 糖尿病患者神经组织内肌醇含量减少,磷脂酰肌醇代谢减弱,蛋白激酶C活性降低,影响Na + -K + -ATP酶的磷酸化而致活性降 低,细胞内Na + 增多,跨膜Na + 浓度梯度降低,导致神经传导速度减慢,角膜感觉减退.
4.5 其他 糖尿病患者神经内肽类物质含量的降低可使三叉神经营养作用部分丧失,从而导致糖尿病眼表发生病变 [17] .Takahashi等 [18] 经体内及体外实验证实,在糖尿病模型小鼠角膜上皮愈合过程中基质金属蛋白酶的活性增强,提示其在糖尿病角膜病变中起一定作用.Ramos-Remus等 [19] 认为糖尿病患者泪液分泌减少与自主神经系统功能失调有关,与Sjogren's综合征引起泪液分泌减少机制不同.
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