糖尿病白内障中Mcl-1调控线粒体凋亡及G2/M周期阻滞的分子机制及功能研究

Diabetic cataract is one of the most serious early intraocular complications of diabetes. The proliferation and apoptosis of lens epithelial cells are critical for maintaining the normal function of the lens. The anti-apoptosis protein Mcl-1 is an important molecule taking part in many cellular processes, but the role of Mcl-1 in diabetic cataract remains unkown. Our previous study indicates that cell apoptosis and G2/M arrest participated in the survival inhibition of the lens epithelial cells induced by high glucose. At the same time, the level of Mcl-1 was decreased while glucose concentration increasing. Overexpression of the Mcl-1 could inhibit the apoptosis and G2/M arrest induced by high glucose in lens epithelial cells. To sum up, we propose a hypothesis as follows; decreased expression of Mcl-1 activates the mitochondrial apoptosis pathway, G2/M arrest and oxidative, lead to apoptosis of lens epithelial cells and then diabetic cataract finally. Our purpose is to understand the role of Mcl-1 in the diabetic cataract by using the cell and molecular biology technology. The knowledge about Mcl-1 would provide us a new method to understand the molecular mechanism of diabetic cataract. Meanwhile, our finding could not only provide a novel potential target for the progress and prognosis of diabetic cataract, but also a new breakthrough for the development of non-surgical treatments for diabetic cataract.

糖尿病白内障是糖尿病最严重的早期眼内并发症之一。晶状体上皮细胞的增殖和凋亡对于维持晶状体正常功能至关重要。抗凋亡蛋白Mcl-1调控多种细胞进程，但在糖尿病白内障中的作用尚缺乏文献报道。我们前期的实验发现，细胞凋亡和G2/M细胞周期阻滞参与高糖培养诱导的晶状体上皮细胞存活抑制。同时实验发现，Mcl-1的表达随着葡萄糖浓度的升高而明显降低。过表达Mcl-1抑制高糖培养诱导的晶状体上皮细胞凋亡和G2/M细胞周期阻滞。因此，我们提出以下假说：糖尿病白内障患者晶状体上皮细胞中，下调的Mcl-1激活了线粒体途径凋亡、G2/M周期阻滞、氧化应激等多条信号通路，最终引起上皮细胞凋亡和晶状体混浊。我们的目的是借助细胞生物学和分子生物学技术，了解Mcl-1在糖尿病白内障中的表达及功能，为了解糖尿病白内障分子机制提供新的思路，为糖尿病白内障的进展和预后提供新的指标，为非手术治疗方式的开发提供新的突破点。

糖尿病白内障是糖尿病最严重的早期眼内并发症之一。晶状体上皮细胞的增殖和凋亡对于维持晶状体正常功能至关重要。抗凋亡蛋白Mcl-1调控多种细胞进程，但在糖尿病白内障中的作用尚缺乏文献报道。本研究发现，细胞凋亡、G2/M细胞周期阻滞参和ROS与高糖培养诱导的晶状体上皮细胞存活抑制。同时实验发现，Mcl-1的表达随着葡萄糖浓度的升高而明显降低。过表达Mcl-1抑制高糖培养诱导的晶状体上皮细胞凋亡和G2/M细胞周期阻滞。本研究借助细胞生物学和分子生物学技术，验证了一种糖尿病白内障可能的发病机制：糖尿病白内障患者晶状体上皮细胞中，下调的Mcl-1激活了线粒体途径凋亡、G2/ M周期阻滞、氧化应激等多条信号通路，最终引起上皮细胞凋亡和晶状体混浊。本研究为了解Mcl-1在糖尿病白内障中的表达及功能，为了解糖尿病白内障分子机制提供新的思路，为糖尿病白内障的进展和预后提供新的指标，为非手术治疗方式的开发提供新的突破点。