Ghrelin拮抗人晶状体上皮细胞及组织氧化损伤中PI3K-AKT-mTOR信号通路的作用及机制研究

Highly reactive free radicals reaction induced by oxidative stress injury lead to the lesion of lens epithelial cells (LECs) and lens tissue. The study on alleviating lens opacity caused by free radical production has become one of research hotspots in the field of cataract. Gherlin is an endogenous active peptide which can inhibit cell oxidative damage and apoptosis. Our previous work showed that Ghrelin regulated the expression of antioxidant enzymes to suppress apoptosis of LECs and lens opacity of rats induced by H2O2. In recent years, studies have shown that Ghrelin combined with specific receptor GHSR-1a to activate intracellular signal transduction pathways so that restrained various cellular oxidative damage and apoptosis. This project intends to select LECs apoptosis induced by H2O2 and rats cataract models as research object. Molecular biology methods is utilised to alter the expression of GHSR-1a and AKT after giving Gherlin exogenously.Then observe oxidative damage of lens epithelial cell and changes ofapoptosis index, clarify new mechanisms of Gherlin on easing lens injury so as to provide new theoretical basis in the prevention and treatment of cataract.

氧化应激损伤产生的高活性自由基反应会引起晶状体上皮细胞（LECs）及组织损伤。如何减轻自由基产物导致的晶状体混浊已经成为白内障领域的研究热点之一。生长激素释放多肽（Gherlin）是一种抑制细胞氧化损伤、凋亡的内源性活性肽。我们前期工作表明Ghrelin通过改变LECs抗氧化酶的表达，从而抑制H2O2诱导的LECs凋亡和大鼠晶状体混浊。近年来研究表明，Ghrelin通过与特异性受体GHSR-1a结合来激活细胞内相应信号转导通路，进而抑制多种细胞氧化损伤及凋亡。本项目拟通过以H2O2诱导的LECs凋亡及大鼠白内障模型为研究对象，外源性给予Gherlin后，利用分子生物学方法改变GHSR-1a及AKT 的表达，观察晶状体上皮细胞氧化损伤及凋亡指标变化，阐明Gherlin减轻晶状体损伤的新机制，从而为探寻防治白内障药物提供新的理论依据。

氧化应激损伤产生的高活性自由基反应会引起晶状体上皮细胞（LECs）及组织损伤。如何减轻自由基产物导致的晶状体混浊已经成为白内障领域的研究热点之一。生长激素释放多肽（Gherlin）是一种抑制细胞氧化损伤、凋亡的内源性活性肽。我们前期工作表明Ghrelin通过改变LECs抗氧化酶的表达，从而抑制H2O2诱导的LECs凋亡和大鼠晶状体混浊。高糖诱导的氧化应激损伤同样引起人们的关注。在本项目资助下，我们对氧化损伤的晶状体上皮细胞、晶状体组织及视网膜进行了进一步研究，证实Ghrelin可以抑制体外培养晶状体上皮细胞氧化损伤及凋亡，抑制晶状体组织损伤。随着研究内容的不断深入，我们从更深层次出发，对ghrelin的生物学功效进一步探讨，Ghrelin治疗糖尿病大鼠后，能有效延缓糖尿病大鼠视网膜病变的进程，其作用机制与降低氧化应激水平、抑制炎症反应相关。我们的发现探索出了一种经济有效的非手术防治白内障新途径，是应对我国人口老龄化的重要措施，具有潜在的应用前景和广泛的社会效益。