Sosne Gabriel, Szliter Elizabeth A, Barrett Ronald, Kernacki Karen A, Kleinman Hynda, Hazlett Linda D
Eye Care Services Department, Henry Ford Hospital, 2799 West Grand Boulevard K10, Detroit, MI 48202, U.S.A.
Exp Eye Res. 2002 Feb;74(2):293-9. doi: 10.1006/exer.2001.1125.
Previously, thymosin beta 4 (Tbeta(4)) was found to promote wound healing in full thickness skin wounds and heptanol debrided corneas. Here, the effect of Tbeta(4) was examined treatment on corneal wound healing and inflammation in vivo after alkali injury, a more severe wound of the eye. Corneas from 129 Sv mice were chemically burned with a 2 mm disc soaked in 1 N NaOH for 30 sec. Eyes were irrigated copiously with phosphate buffered saline (PBS) and then treated topically with either Tbeta(4) (5 microg/5 microl PBS) or 5 microl PBS twice daily. Animals were killed, the eyes were enucleated, fixed and embedded in plastic resin or prepared for mRNA analysis. Mouse corneas topically treated with 5 microg of Tbeta(4) twice daily after alkali injury demonstrated accelerated re-epithelialization at all time points and decreased polymorphonuclear leukocyte (PMN) infiltration at 7 days post injury (p.i.) when compared to PBS-treated controls. mRNA transcript levels were decreased several fold for interleukin (IL)-lbeta, and the chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, MIP-2 and monocyte chemoattractant protein (MCP)-1 from 1 to 7 days after injury in the Tbeta(4)- vs. PBS-treated corneas. Thus, Tbeta(4) may provide a new clinical treatment for severe traumatic corneal wound disorders by promoting rapid corneal wound healing and decreasing both PMN infiltration and inflammatory cytokine and chemokine mRNA levels.
此前发现，胸腺素β4（Tbeta(4)）可促进全层皮肤伤口和庚醇清创角膜的伤口愈合。在此，研究了Tbeta(4)对碱烧伤（一种更严重的眼部伤口）后体内角膜伤口愈合和炎症的治疗效果。用浸泡在1 N NaOH中的2 mm圆盘对129 Sv小鼠的角膜进行化学烧伤30秒。用磷酸盐缓冲盐水（PBS）大量冲洗眼睛，然后每天两次局部给予Tbeta(4)（5微克/5微升PBS）或5微升PBS。处死动物，摘除眼球，固定并包埋在塑料树脂中或准备进行mRNA分析。与PBS处理的对照组相比，碱烧伤后每天两次局部给予5微克Tbeta(4)的小鼠角膜在所有时间点均显示上皮再形成加速，且在损伤后7天多形核白细胞（PMN）浸润减少。在Tbeta(4)处理组与PBS处理组的角膜中，从损伤后1至7天，白细胞介素（IL）-1β以及趋化因子巨噬细胞炎性蛋白（MIP）-1α、MIP-1β、MIP-2和单核细胞趋化蛋白（MCP）-1的mRNA转录水平降低了数倍。因此，Tbeta(4)可能通过促进角膜伤口快速愈合以及降低PMN浸润、炎性细胞因子和趋化因子mRNA水平，为严重创伤性角膜伤口疾病提供一种新的临床治疗方法。
