Notch信号通路与兔深Ⅱ度烧伤创面血管相关因子的表达

Expression of vascular relevant factors in rabbits with deep Ⅱ degree burn based on the Notch signaling pathway

目的:探讨Notch信号通路与兔深Ⅱ度烧伤模型创面血管相关因子表达的关系。方法:120只新西兰大白兔,随机分为阻滞剂组、模型组、对照组。其中阻滞剂组于造模前1 d及造成深Ⅱ度烫伤后连续14 d按2 mg/kg注射γ-分泌酶阻滞剂(gamma-secretase inhibitor,GSI),每天1次;模型组同期注射生理盐水,每天1次;对照组不予造模,余同模型组。每组分别于第3,7,14,21,28天随机抽取8只处死,采用免疫组织化学法检测血管内皮生长因子(vascular endothelial growth factor,VEGF)、血管内皮细胞生长因子受体2(vascular endothelial growth factor receptor 2,VEGFR-2)、基质金属蛋白酶2(matrix metalloprotein 2,MMP-2)、基质金属蛋白酶9(matrix metalloprotein 9,MMP-9)的表达。结果:模型组与阻滞剂组造模后21 d内VEGF和VEGFR-2的表达逐步上升,第21天后有所下降,而MMP-2和MMP-9的表达逐步下降,第21天后有所上升,与对照组比较,差异均有统计学意义(P<0.05);各时间点模型组VEGF和VEGFR-2的表达均高于阻滞剂组,MMP-2和MMP-9的表达均低于阻滞剂组,差异具有统计学意义(P<0.05),阻滞剂组在造模后21 d内,VEGFR-2的表达与VEGF呈正相关,而MMP-2和MMP-9则与VEGF呈负相关。结论:在兔深Ⅱ度烧伤模型创面中,Notch信号通路被阻滞能够减弱创面血管生成因子VEGF和VEGFR-2的表达,而上调抑制因子MMP-2和MMP-9的表达。

Objective： To investigate the relationship between the Notch signaling pathway and expression of vascular relevant factors in rabbit deep Ⅱ degree burn model.Methods： A total of 120 New Zealand white rabbits were randomly divided into a block group,a model group, and a control group. The block group was injected 2 mg/kg γ-secretase inhibitor （GSI） once a day at 1 d before the model establishment, and 1-14 d after the deep II degree burns model establishment. The model group were injected physiological saline at the same time.The control group was only injected with the same amount of saline. The expressions of vascular endothelial growth factor （VEGF）, vascular endothelial growth factor receptor 2 （VEGFR-2）,matrix metalloprotein 2 （MMP-2） and matrix metalloprotein 9 （MMP-9） were detected by immunohistochemistry. Results： The expressions of VEGF and VEGFR-2 in the model group and the block group were significantly increased within 21 days after modeling, while decreased after 21 days; the expressions of MMP-2 and MMP-9 were decreased within 21 days after modeling, while increased after 21 days, with significant differences compared with the control group （P〈0.05）. The expressions of VEGF and VEGFR-2 in the model group were higher than that in the block group, and the expressions of MMP-2 and MMP-9 were lower than those in the block group （P〈0.05）. The expression of VEGFR-2 was positively correlated with VEGF, while MMP-2 and MMP-9 were negatively correlated with VEGF within 21 days after modeling.Conclusion： In the rabbit deep II degree burn model, the Notch signaling pathway was blocked to attenuate the expressions of VEGF and VEGFR-2, and to up-regulate the expressions of MMP-2 and MMP-9.