损伤角膜修复重建中的ROCK抑制剂:促进角膜细胞增殖、迁移和黏附

Role of ROCK inhibitor in corneal reconstruction: promoting the proliferation, migration and adhesion of keratocytes

背景:随着人们对Rho/ROCK通路的生物学功能的了解的不断加深,新的ROCK抑制剂不断被发现,且ROCK抑制剂在角膜细胞存活、增殖和迁移中表现出良好的促进效果,ROCK抑制剂的研究能为再生医学和临床细胞移植提供更多的良好供体材料或种子细胞。目的:总结并探讨ROCK抑制剂Y-39983和Y-27632在角膜病的治疗和应用的研究进展。方法:应用计算机检索Pub Med数据库和中国知网数据库内相关文章,检索时间为2008至2015年,检索词为"corneal endothelial cell,corneal epithelial cell,ROCK inhibitor,Y-39983,Y-27632,ROCK抑制剂,角膜",从中筛选出与主题相关的部分文献。结果与结论:初检得到264篇文章,按主题相关性对文献进一步筛选,最终纳入45篇文章进行讨论。应用到眼科的ROCK抑制剂主要有两种:Y-27632和Y-39983,两者的应用主要还是基础研究与临床试验阶段。Y-27632可促进角膜缘上皮干细胞增殖及提高冻存复苏后的活性;Y-39983作为一种新型的ROCK抑制剂,其比Y-27632更有效地抑制ROCK激酶的活性,从而能更有效地促进角膜内皮的愈合。目前ROCK抑制剂在角膜治疗的研究较多,但是没有建立一种稳定的获得种子细胞的方法,每一种治疗方法都各有优缺点,而克服这些缺点以及找到快速稳定获得种子细胞的方法是今后的发展方向。

BACKGROUND： With the deepen understanding on the biological function of Rho/ROCK pathway, new ROCK inhibitors continue to be discovered, and ROCK inhibitors show good promoting effects on the survival, proliferation and migration of keratocytes. Research on ROCK inhibitors will provide more donor materials or seed cells for regenerative medicine and clinical cell transplantation.OBJECTIVE： To summarize and explore the progress in the treatment and application of corneal disease using the ROCK inhibitors Y-27632 and Y-39983.METHODS： The PubMed database and CNKI database were retrieved by computer to search the relevant literature published between 2008 to 2015 using the key words of ＂corneal endothelial cell, corneal epithelial cell,ROCK inhibitor, Y-39983, Y-27632＂ in English and Chinese, respectively. Relevant articles in line with the theme were screened and analyzed.RESULTS AND CONCLUSION： Totally 264 papers were initially searched. At last, 45 papers were selected. Currently there are two main ROCK inhibitors： Y-27632 and Y-39983, but both of which are still in basic research stage and clinica testing stage. Y-27632 promotes the proliferation and activity of corneal epithelial stem cell after resuscitation; Y-39983 as a novel ROCK inhibitor can be better to inhibit Rho kinases activity than Y-27632, thereby more effectively promoting the healing of the corneal endothelium. There are many studies on the application of ROCK inhibitors in corneal treatment, but not a stable method established to obtain seed cells. Each method has its own advantages and disadvantages, and how to overcome these disadvantages and to find fast and stable access to seed cells is the future direction of development.