·糖尿病基础研究·

　　于虎 马瑞珏 张朔杨 李艳 车永哲 许松山

　　基金项目：国家大学生创新实验计划(NK0707)

　　作者单位：300071天津，南开大学医学院神经解剖学教研室(于虎、马瑞珏、张朔杨、李艳、车永哲);北京诺思兰德生物技术股份有限公司(许松山)

　　通讯作者：车永哲，E-mail:cheli@nankai.edu.cn

　　【摘要】 目的 研究胸腺素 β4(Tβ4)调节血管内皮生长因子(VEGF)和层粘连蛋白5(LN-5)的表达，探讨其促进糖尿病大鼠皮肤损伤愈合的机制。 方法 60只雄性 SD大鼠建立糖尿病大鼠全层皮肤损伤模型(D=8mm)，随机分为糖尿病对照(DM)组和Tβ4治疗组[又分为低(L-Tβ4)、中(M-Tβ4)、高(H-Tβ4)3个剂量组]。计算皮肤愈合率和表皮迁移率。一侧伤口进行 HE染色，弹力纤维、胶原纤维、网状纤维三联染色和VEGF、LN-5免疫组化染色;另一侧伤口进行 LN-5 ELISA 测定。 结果 M-Tβ4 和 H-Tβ4 组各时间点伤口愈合率均较DM组高(P<0?05或P<0?01);损伤后10d M-Tβ4 和 H-Tβ4组的表皮迁移率高于DM组(P<0?01)。Tβ4治疗组肉芽组织中 VEGF 表达较多、阳性血管较丰富，LN-5在表皮基底细胞和基底膜早期表达;损伤后2d 和 10d Tβ4治疗组 LN-5含量较高，损伤后4d较低。 结论 Tβ4可促进糖尿病大鼠皮肤损伤愈合，其机制可能与调节VEGF和LN-5表达有关。

　　【关键词】胸腺素β4; 糖尿病; 损伤愈合; 血管内皮生长因子; 层粘连蛋白5

　　doi:10.3969/j.issn.1006-6187.2011.01.016

　　Thymosin beta 4 regulates the expression of VEGF and laminin-5 in accelerating skin wound healing in diabetic rat

　　YU Hu, MA Rui-jue, ZHANG Shuo-yang, et al.Department of Neuroanatomy,Medical School of Nankai University, Tianjin 300071, China

　　Corresponding author: CHE Yong-zhe, E-mail:cheli@nankai.edu.cn

　　【Abstract】 Objective To study the effects of thymosin β4 (Tβ4) on regulation expression of VEGF and LN-5 and on accelerating skin wound healing in diabetic rat.? Methods Two full thickness punch wounds(D=8mm)were made at the costovertebral angle on dorsal surface of each adult male diabetic SD rat weighing 200～250 g.60 diabetic wound models were distributed randomly into the control group (n=15) and the treatment group (n=45), which was subdivided into low(Tβ4 0?5 μg/50 μl), medium(Tβ4 5 μg/50 μl)and high(Tβ4 15 μg/50 μl)dose groups.The skin wound healing rate and the epidermis migration rate were calculated.Skin sections were applied with H-E stain, trichrome stain and VEGF, LN-5 immunostains.LN-5 concentration was measured by ELISA assay. Results Compared with control group, there was a significant increase of wound healing rate in the medium and high dose group at each time point(P<0?05).Epidermis migration rate of the medium and high dose group was higher than control group(P<0?01).Immunostain showed there was more VEGF expression and positive blood vessels in the granulation in the treatment group, LN-5 was expressed in the epidermis and the epidermal basement membrane at 2 day.LN-5 ELISA assay showed that LN-5 content was higher in 2 days or 10 days treatment group than in control group,but lower in 4 day group than in than control group. Conclusions Tβ4 may regulate the expression of VEGF and LN-5 and then promotes reepithelization and angiogenesis,finally accelerating skin wound healing in diabetic rat.

　　【Key words】Thymosin beta 4; Diabetes; Wound healing;Vascular endothelial growth factor; Laminin-5