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

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。

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

Objective To investigate whether or not vascular endothelial growth factor ( VEGF) and cysteine-containing aspartate-specific proteases-3 (Caspase-3) to take part in secondary brain injury after periventricular-intravent-ricular hemorrhage ( PV-IVH) in premature rabbits. Methods Premature rabbit models of PV-IVH were established u-sing 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 apopto-sis 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 con-trol 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 differences in Caspase-3 positive expression rate between each 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 difference 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 treat-ment showed no significant difference compared with those in control group (P>0. 05). In PV-IVH group, average rate of apoptosis 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 be-tween each two time points ( P >0. 05 ) . Conclusion After PV-IVH, number of VEGF positive-cells is increased, which indicates that VEGF participates in the secondary brain injury and possibly plays the role of brain protection;num-bers of positive-cells and apoptosis of Caspase-3 are significantly increased, and expressions of them tend to be in uni-formity, which indicates in that Caspase-3 participates in the secondary brain injury.