【摘要】 目的　建立单侧缺氧缺血性脑损伤 (HIBD)动物模型 ,研究胰岛素样生长因子 1(IGF 1)对HIBD的影响和可能机制。　方法　选择健康 7日龄Wistar大鼠 12 0只 ,建立HIBD模型 ,随机分成假手术组、HIBD组、HIBD后 0 .2mg/kg人基因重组IGF 1干预组 (RH IGF 1组 )、0 .0 6 6mg/kg人基因重组IGF 1干预组 (SRH IGF 1组 )及盐水对照组 (对照组 )。各组按观察时段进一步分为 2 4、4 8、72h组 ,每组 8只。各组于规定时刻观测脑形态学改变、谷氨酸 (Glu)含量、凋亡细胞计数、Bcl 2蛋白表达。　结果　 (1)HIBD 4 8h组Glu(116 2 .2± 10 8.1)mg/kg ,较假手术组(75 0 .9± 5 3.4 )mg/kg明显升高 (P <0 .0 5 ) ;HIBD组凋亡细胞计数 [2 4h :(7.6± 1.9) % ,4 8h(12 .6±1.2 ) % ,72h :(13.8± 0 .9) % ],较假手术组 [2 4h(2 .0± 0 .2 ) % ,4 8h(2 .0± 0 .3) % ,72h(2 .0±0 .2 ) % ]明显增加 (P均 <0 .0 5 )。 (2 )与对照组相比 ,RH IGF 1组脑组织病变减轻 ;干预 4 8h组Glu[SRH IGF 1组 (781.4± 5 4 .2 )mg/kg ,RH IGF 1组 (74 0 .5± 4 6 .6 )mg/kg],较对照组 (112 6 .6± 4 8.0 )mg/kg明显降低 (P均 <0 .0 5 ) ;RH IGF 1组凋亡细胞计数 [2 4h :(3.6± 0 .9) % ,4 8h(8.2± 2 .2 ) % ,72h(9.4± 1.4 ) % ],较对更多还原

【Abstract】 Objective To evaluate the protective effect of insulin-like growth factor-1 (IGF-1) on hypoxic-ischemic brain damage (HIBD) in newborn rats. Methods One hundred and twenty 7-day-old Wistar rats were randomly divided into sham control,HIBD,HIBD treated with 0.2 mg/kg RH-IGF-1 ,HIBD treated with 0.066 mg/kg RH-IGF-1,and normal saline control groups. Those groups were further divided into 24 h、 48 h and 72 h groups respectively after damage with 8 rats in each group. The histological feature,levels of glutamate (Glu) and apoptosis,and expression of Bcl-2 protein in brain were observed in each group. Results (1) Level of Glu in HIBD 48 h group (1162.2±108.1) mg/kg and levels of apoptosis in every HIBD groups[24 h: (7.6±1.9),48 h: (12.6±1.2),72 h: (13.8±0.9) %] are significantly higher than those in sham groups of the same time,[Glu: (750.9± 53.4) mg/kg and apoptosis: 24 h: (2.0±0.2)%,48 h: (2.0±0.3)%,72 h: (2.0± 0.2)%] respectively ( P <0.05). (2) Treated with RH-IGF-1,the number of dendrite and Nissl’s bodies of neuron in RH-IGF-1 groups get more and levels of Glu in every RH-IGF-1 treated 48 h groups [SRH-IGF-1 group:(781.4±54.2),RH-IGF-1 group:(740.5±46.6 ) mg/kg] and levels of apoptosis in RH-IGF-1 treated groups [24 h:(3.6±0.9),48 h:(8.2±2.2),72 h:(9.4±1.4) %] are significantly less than those in the same time NS control groups,[Glu:(1126.6±48.0 )mg/kg and apoptosis: 24 h:(7.6±1.9),48 h:(12.6±1.6),72 h:(13.9±0.4) %] respectively ( P <0.05);Expression of Bcl-2 protein in each RH-IGF-1 treated 48 h,72 h groups (71.4%,71.4%)are significantly higher than those in the same time in NS control group (14.2%,14.2%) respectively ( P <0.05 ). Conclusions (1) IGF-1 will significantly reduce the Glu level in the brain with HIBD. (2)IGF-1 will reduce the apoptosis,increase the expression of Bcl-2 protein. IGF-1 has potential dose relying therapical effect on HIBD.更多还原