经鼻给予胰岛素样生长因子1对新生大鼠缺氧缺血性脑损伤的影响

Effect of intranasal delivery of insulin-like growth factor 1 on neonatal rats with hypoxic-ischemic brain damage

目的:胰岛素样生长因子1具有非选择性神经营养作用,选择经鼻外源性中枢给药方式,观察其对新生大鼠缺氧缺血性脑损伤的保护作用及其机制。方法:实验于2000-01/03在南京医科大学儿科研究所实验室完成。取28只7日龄新生大鼠随机分为对照组,给药组和假手术组3组。给药组于缺氧后经鼻腔滴入胰岛素样生长因子12.5μg(溶于生理盐水0.1mL中);对照组于缺氧缺血性脑损伤后给予等量的生理盐水经鼻腔滴入;假手术组仅分离颈总动脉,不结扎不缺氧。24h后处死动物取脑组织,应用组织学方法检查损伤部位变性神经细胞计数,应用免疫组化法检查脑组织半胱氨酸天冬氨酸蛋白酶3的表达,评估胰岛素样生长因子1的脑保护作用。结果:脑组织半胱氨酸天冬氨酸蛋白酶3蛋白表达水平:假手术组个别皮质区域有少量表达。与对照组(7.27±0.48)相比,用药组半胱氨酸天冬氨酸蛋白酶3(2.03±0.64)表达减少(P<0.01),神经细胞总数增加(P<0.01),变性/坏死神经细胞数减少(P<0.01)。结论:鼻腔滴入胰岛素样生长因子1可能通过降低缺氧缺血性脑损伤脑组织中半胱氨酸天冬氨酸蛋白酶3表达,从而对缺氧缺血性脑损伤脑组织损伤产生保护作用。

AIM:Insulin like growth factor I(IGF 1) has the selective function on nourishing the nerve,intranasal delivery of IGF 1 was chosen.In this study we observed the protective function on neonatal rats with hypoxic ischemic brain damage(HIBD) and the mechanism. METHODS: The experiment was finished in the Laboratory of Department of Pediatrics, Huaian First Hospital of Nanjing Medical University,from January to March 2003. Twenty eight neonatal rats of 7 days were randomly divided into three groups: control group,drug treated group,and sham operated group.Drug treated group and control group received respectively nasal dropped with IGF 1 12.5 μg(dissolved with 0.1 mL saline) and 0.1 mL saline immediately after hypoxia,and control group only split common carotid artery without deligation and hypoxia.All animals were killed at 24 hours after hypoxia.Histopathology was used to detect the number of degenerative neurocytes.Immunocytochemisty was used to detect the expression of Caspase 3 protein and evaluate the protective function of IGF 1. RESULTS:As compared with control group (7.27±0.48), the expression of Caspase 3 protein in drug treated group (2.03±0.64) was obviously decreased (P< 0.01 ),and the number of neurocytes increased (P< 0.01), and degenerative neurocytes decreased (P< 0.01). CONCLUSION:Nasal treated with IGF 1 may reduce the expression of Caspase 3 protein in brain tissue in neonatal rats with HIE, and may have a neuroprotective function.