选择性环氧合酶2抑制剂尼美舒利抑制皮肤瘢痕形成的研究

背景:尼美舒利是一种选择性环氧合酶2抑制剂,可通过抑制环氧合酶2的合成、抑制前列腺素的合成、白细胞的介质释放等环节影响炎症的发生过程,具有解热、镇痛和抗炎作用。目的:探讨尼美舒利抑制小鼠皮肤瘢痕形成的作用及机制。方法:昆明种小鼠背部脊柱两侧建立皮肤损伤模型,随机分为模型组、25,50,100μmol/L尼美舒利组,切口分别涂抹0.5mL玻璃酸钠凝胶、25,50,100μmol/L尼美舒利玻璃酸钠分散制剂。结果与结论:应用25,50μmol/L尼美舒利可以明显减小瘢痕组织的面积(P<0.01),但100μmol/L尼美舒利却造成损伤面积增大(P<0.05),与模型组相比,不同剂量的尼美舒利治疗的小鼠在创伤形成第3,7,14天环氧合酶2的表达明显降低,且其中50和100μmol/L尼美舒利治疗的小鼠创口微血管的生成速度明显降低(P<0.05),提示尼美舒利可以通过适度下调皮肤修复过程中环氧合酶2的表达,控制微血管的形成,达到抑制病理性瘢痕形成的治疗目的,但剂量过大(100μmol/L)则可抑制创伤的愈合。

Effect of selective cyclooxygenase-2 inhibitor nimesulide on the formation of skin scar

BACKGROUND:Nimesulide is a kind of selective cyclooxygenase-2 inhibitor that can influence the inflammation through inhibiting the synthesis of cyclooxygenase-2 and prostaglandin and the release of leukocytes media,which has antipyretic,analgesic and anti-inflammatory effects.OBJECTIVE:To investigate the inhibition effect and mechanism of selective cyclooxygenase-2 inhibitor nimesulide on the formation of skin scar in mice.METHODS:The models of skin wound were established and divided into four groups:model group,25 μmol/L nimesulide group,50 μmol/L nimesulide group and 100 μmol/L nimesulide group.The incisions were treated with 0.5 mL sodium hyaluronate,25,50 and 100 μmol/L nimesulide sodium hyaluronate dispersed preparation respectively.RESULTS AND CONCLUSION:Nimesulide have significant impact on the skin wound healing,the scar area was significantly decreased in 25 μmol/L nimesulide group and 50 μmol/L nimesulide group(P < 0.01),but the scar area in the 100 μmol/L nimesulide group was increased(P < 0.05).The expressions of cyclooxygenase-2 in the nimesulide groups were significantly decreased at 3,7 and 14 days after wound formation when compared with the model group,and the microvessel density in the 50 μmol/L nimesulide group and 100 μmol/L nimesulide group was significantly decreased(P < 0.05).Appropriate application of nimesulide has a positive effect on surgical wound in mice,and can reduce the pathological scar formation.But the overdose of nimesulide(100 μmol/L) can inhibit the healing of the wounds.The mechanism may be to decrease the expression of cyclooxygenase-2 and the formation of capillary vessels.