VEGF及Caspase-3在早产儿脑室周围-脑室内出血后继发脑损伤中的作用

Effect of VEGF and Caspase-3 on Secondary Brain Injury after Periventricular-Intraventricular Hemorrhage in Premature Rabbits

目的探讨血管内皮生长因子(VEGF)和天冬氨酸特异性半胱氨酸蛋白酶-3(Caspase-3)是否参与早产儿脑室周围-脑室内出血(PV-IVH)后的继发性脑损伤。方法采用丙三醇腹腔注射法(Georgiadis P)制作早产兔PV-IVH模型,分为PV-IVH模型组(18只)及对照组(18只)。两组于处理后24、48、72 h 3个时间段分别检测VEGF、Caspase-3阳性细胞、凋亡细胞表达。结果 PV-IVH模型组VEGF阳性细胞数在不同时相均明显多于对照组,PV-IVH模型组VEGF平均阳性细胞表达率在处理后24、48、72 h均高于对照组(P<0.05,P<0.01),组内48、72 h均低于24 h(P<0.01)、72 h低于48 h(P<0.05),对照组VEGF平均阳性细胞表达率在处理后24、48、72 h两两比较,差异无统计学意义(P>0.05);PV-IVH模型组Caspase-3阳性细胞数在不同时相均明显多于对照组,PV-IVH模型组Caspase-3平均阳性细胞表达率在处理后24、48、72 h均高于对照组(P<0.01),组内48 h高于24 h(P<0.01)、72 h低于24、48 h(P<0.01),对照组Caspase-3阳性细胞的表达率在处理后24、48、72 h两两比较,差异无统计学意义(P>0.05);PV-IVH模型组凋亡细胞数在处理后24、48 h明显多于对照组,处理后72 h凋亡细胞数与对照组比较无明显变化,PV-IVH模型组凋亡细胞平均表达率在处理后24、48 h均较高于对照组(P<0.01),处理后72 h与对照组相比,差异无统计学意义(P>0.05),组内48 h高于24、72 h(P<0.01)、72 h低于24 h(P<0.01),对照组脑组织凋亡细胞的平均表达率在处理后24、48、72 h两两比较,差异无统计学意义(P>0.05)。结论 PV-IVH后,VEGF阳性细胞数目显著增加,提示VEGF参与了PV-IVH后继发性脑损伤,可能发挥了脑保护作用;Caspase-3阳性细胞、凋亡细胞数目明显增多,且Caspase-3阳性细胞与凋亡细胞表达趋势一致,提示Caspase-3参与PV-IVH后继发性脑损伤。

Objective To investigate whether or not vascular endothelial growth factor （VEGF） and cysteinecontaining aspartate-specific proteases-3 （ Caspase-3 ） to take part in secondary brain injury after periventrieular-intraventrieular hemorrhage （PV-IVH） in premature rabbits. Methods Premature rabbit models of PV-IVH were established using Glycerin peritoneal injection （Georgiadis P）, and the rabbits were divided into PV-IVH group （n = 18） and control group （ n = 18）. At 24 h, 48 h and 72 h after treatment in the two groups, positive-cell expressions of VEGF and apoptosis expressions were detected. Results In PV-IVH group, numbers of VEGF positive-cells at different time points were bigger, and average VEGF positive expression rates at 24 h, 48 h and 72 h after treatment were higher than those in control group （P 〈 0. 05, P 〈 0.01 ） ; average VEGF positive expression rates at 48 h and 72 h after treatment were lower than that at 24 h after treatment （P 〈 0.01 ） , and the rate at 72 h after treatment was lower than that at 48 h （ P 〈 0.05 ）. In control group, there were no significant differences in VEGF positive expression rate between each two time points （P 〉 0.05 ）. In PV-IVH group, numbers of Caspase-3 positive-cells at different time points were more, and average VEGF positive expression rates at 24 h, 48 h and 72 h after treatment were higher than those in control group （P 〈 0. 01） ; average Caspase-3 positive expression rate at 48 h after treatment was higher than that at 24 h after treatment （ P 〈 0. 01 ） . and the rate at 72 h after treatment were lower than those at 24 h and 48 h after treatment （ P 〉 0. 01 ） . in control group, there were no significant ditt＂erences in Caspase-3 positive expression rate between eaeh two time points （ P 〉 0.05 ）. In PV-IVH group, apoptosis numbers at 24 h and 48 h after treatment were significantly higher, while the number at 72 h after treatment showed no significant diftercnce compared with those in control group, and average rate of apoptosis expression at 24 h and 48 h after treatment were significantly higher （ P 〈 0.01 ） , but the rate at 72 h after treatment showed no significant difference compared with those in control group （ P 〉 0.05）. In PV-IVH group, average rate of apoplosis expression at 48h was higher than those at 24 h and 72 h （ P 〈0.01 ） , and the rate at 72 h was lower than that at 24 h （ P 〈 0. 01 ）. In control group, there were no significant differences in average rate of apoptosis expression between each two time points （ P 〉 0.05 ）. Conclusion After PV-IVH, number of VEGF positive-eells is increased, which indicates thai VEGF participates in the secondary brain injury a,nt possibly plays the role of brain protection ; numbers of positive-cells and apoptnsis of Caspase-3 are significantly increased, and expressions of them tend to be in uniformity, which indicates in that Caspase-3 participates in the secondary brain injury.