胸腺素β4调节皮肤创伤愈合时ICAM-1及VEGF的表达

ICAM-1 and VEGF alterations revealed by recombinant thymosin 4 in rat skin wound healing

目的研究重组胸腺素β4(thymosin 4,Tβ4)调节ICAM-1和VEGF的表达促进创伤愈合的机制。方法成年雄性SD大鼠,体质量200～250 g,制备全层皮肤缺损模型。动物随机分为PBS对照组和Tβ4 2μg/50 L组、6μg/50μl组和18μg/50μl组。实验组于模型制备后即刻、每天7:00、19:00伤口表面滴加Tβ4 50μl。对照组滴加等量PBS液。造模后2、4、7 d取材染色。结果H-E染色显示各组有不同程度的炎症反应和肉芽组织形成。Tβ4处理后,ICAM-1阳性表达增多,2 d时2、18μg组表达较强(P<0.01),4 d时各组均减弱,18μg组相对较强,7 d时各组表达增强,18μg组最强(P<0.01)。4 d时VEGF阳性最多,7 d时阳性减少,6μg组表达强度保持在较高水平(P<0.05)。结论重组Tβ4可能抑制炎细胞的活化和增殖,调节炎症反应影响ICAM-1、VEGF的表达,促进创伤愈合。

Objective To explore the mechanisms of recombinant thymosiniM （Tβ4） accelerates skin wound healing in rats by regulating the expression change of ICAM-1 and VEGF. Methods Two full thickness 8 mm punch wounds were made on the dorsal surface each side of the grown male rat at the cost overtebral angle, 60 in total divided into control and experimental group randomly. Tβ4 （Beijing Northland Biotech, Beijing） was applied topically at the time of wounding （2, 6, 18 μg in 50μl PBS） and every 12 h post-wounding. Controls received identical amounts of phosphate buffered saline at the same time. The wound healing rate was measured at 2,4,7 d post- wounding, then wound tissue was collected and fixed in 4% paraformaldehyde for 24 h. The paraffin samples were sectioned, and sections from the middle of the wound were stained with hematoxylin and eosin and ICAM-1 ,VEGF immunohistochemistry stain. This experiment was performed twice using five rats for each test condition. The experimental procedure was accord with animal ethical standards. Results It was showed different inflammation and granulation tissue in the groups. With Tβ4 treated, ICAM-1 immuno-positive cells and vessels were the weakest at 4 d post-wounding, higher positive at 2 d post-wounding and the peak positive at 7 d post-wounding while an excess expression in Tβ4 18μg group （P 〈 0. 01 ）. VEGF immunohisto- chemistry stain were showed the peak positive cells and vessels at 4 d post-wounding, decreased at 7 d postwounding and Tβ4 medium dosage group were expressed maintain high level （ P 〈 0. 05 ）. Conclusion Re- combinant T 4 affects the expression of ICAM-1 and VEGF by inhibiting the activation and proliferation of inflammatory cells to regulate inflammation, then promotes the skin wound healing.