姜黄素对大鼠皮肤创面愈合及血管新生的影响和作用机制

Effect and mechanism of curcumin on skin wound healing and angiogenesis in rats

目的探讨姜黄素对大鼠皮肤创面愈合和血管新生的影响及可能作用机制。方法制备全层真皮缺损伤口大鼠,并随机分为模型组、姜黄素低、中、高剂量组,每组各10只,腹腔注射给药,姜黄素低、中、高剂量组分别给予5、15、45 mg/(kg·d)姜黄素,模型组大鼠每日腹腔注射等量0.5%羧甲基纤维素钠,连续14 d。测定各组大鼠创面愈合率;创面组织行HE、Masson及免疫组化染色;酶联免疫吸附(ELISA)试验检测各组大鼠创面组织血管生成素1(Ang-1)、碱性成纤维细胞生长因子(bFGF)水平;实时荧光定量PCR(qRT-PCR)技术检测创面组织血管内皮生长因子A(VEGFA)、血管内皮细胞生长因子受体-2(VEGFR-2)mRNA相对表达量;Western blot法检测创面组织VEGFA、VEGFR-2、Notch1、Jagged1、Hes1蛋白表达情况。结果姜黄素低、中、高剂量组大鼠创面愈合率、血管密度,创面组织Ang-1和bFGF水平、VEGFA和VEGFR-2 mRNA及Notch1、Jagged1、Hes1、VEGFA及VEGFR-2蛋白相对表达量高于模型组(均P<0.05)。组织学染色结果显示,模型组大鼠创面组织再上皮化不明显,炎症细胞严重浸润,胶原蛋白沉积较少,姜黄素低、中、高剂量组大鼠创面组织再上皮化逐渐明显,表皮逐渐增厚,炎性细胞浸润程度逐渐减轻,且胶原蛋白沉积逐渐增加;姜黄素对大鼠皮肤创面的作用效果呈剂量依赖性增强(均P<0.05)。结论姜黄素可促进大鼠创面愈合及血管新生,其作用机制可能与激活Notch信号通路有关。

Objective To investigate the effect of curcumin on skin wound healing and angiogenesis in rats and its possible mechanism.Methods Rats with full-thickness dermal defect were prepared and randomly divided into model group,low-dose,medium-dose and high-dose groups of curcumin,with 10 rats in each group.Curcumin was injected intraperitoneally.The low-dose,medium-dose and high-dose groups of curcumin were given 5,15,45 mg/(kg·d)curcumin respectively.The rats in the model group were injected intraperitoneally with 0.5%sodium carboxymethyl cellulose for 14 days.The wound healing rate of rats in each group was measured;The wound tissue was stained with haematoxylin and eosin staining,Masson and immunohistochemistry;The levels of angiopoietin-1(Ang-1)and basic fibroblast growth factor(bFGF)in the wound tissue of rats in each group were detected by enzyme-linked immunosorbent assay(ELISA);The relative expression of vascular endothelial growth factor A(VEGFA)and vascular endothelial growth factor receptor-2(VEGFR-2)mRNA in wound tissue was detected by real-time quantitative polymerase chain reaction(qRT-PCR);Western blot was used to detect the expression of VEGFA,VEGFR-2,Notch1,Jagged1,Hes1 protein in the wound tissue.Results The wound healing rate,the vascular density and the level of Ang-1 and bFGF,the mRNA of VEGFA and VEGFR-2,the relative expression of Notch1,Jagged1,Hes1,VEGFA and VEGFR-2 protein in wound tissue of rats in low,medium and high dose groups of curcumin were higher than those in the model group(all P<0.05).Histological staining results showed that the reepithelialization of the wound tissue was not obvious in the model group,with severe infiltration of inflammatory cells and less collagen deposition;the reepithelialization of the wound tissue in the low-dose,medium-dose and high-dose groups of curcumin was gradually obvious,with thickened epidermis,reduced inflammatory cell infiltration and increased collagen deposition.The effect of curcumin on skin wounds in rats was enhanced in a dose-dependent manner(all P<0.05).Conclusions Curcumin could promote wound healing and angiogenesis in rats,and its mechanism may be related to the activation of Notch signaling pathway.