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.%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 μD, 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.
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