电刺激小脑顶核对缺氧缺血性脑损伤新生鼠海马神经胶质细胞的影响

Effects of electric stimulation at the cerebellar fastigial nucleus on astrocytes in the hippocampus of neonatal rats with hypoxic-ischemic brain damage

摘要:

目的：探讨电刺激小脑顶核对缺氧缺血性脑损伤（HIBD）新生大鼠海马神经胶质细胞的影响及可能机制。方法：新生 7 日龄 Sprague-Dawley 大鼠 180 只随机分为假手术组（对照组）、模型组及电刺激组，每组各 60 只。参照 Rice-Vennucci 法制备 HIBD 模型，电刺激组大鼠于造模后 24 h 开始给予电刺激治疗，每日1次，每次30 min，对照组及模型组不予电刺激，相应时段仅予捕捉固定。各组分别于电刺激 3 d、7 d、14 d、21 d取海马组织，免疫组化观察胶质纤维酸性蛋白（GFAP）表达；电镜观察胶质细胞超微结构变化。结果：免疫组化显示模型组及电刺激组 GFAP 的表达在 3 d 时较对照组即有升高，7 d 达到高峰，在14 d、21 d 时表达仍较对照组高，电刺激组 GFAP 的表达在各时间点均较模型组低；电镜发现模型组神经胶质细胞水肿明显，细胞器减少，电刺激组较之肿胀较轻，且细胞器完整。结论：电刺激可抑制神经胶质细胞的过度增生，减轻缺氧缺血后细胞的结构性损伤。

Abstract:

OBJECTIVE: To study the effects of electric stimulation at the cerebellar fastigial nucleus on astrocytes in the hippocampus of neonatal rats with hypoxic-ischemic brain damage (HIBD) and the possible mechanism. METHODS: One hundred and eighty 7-day-old neonatal Sprague-Dawley rats were randomly divided into three groups: sham-operation (control group) and HIBD with and without electric stimulation (n=60 each). The HIBD model of neonatal rats was prepared by the Rice-Vennucci method. Electric stimulation at the cerebellar fastigial nucleus was given 24 hrs after the operation in the electric stimulation group once daily and lasted for 30 minutes each time. The other two groups were not subjected to electric stimulation but captured to fix in corresponding periods. Rats were sacrificed 3, 7, 14 and 21 days after stimulations to observe the glial fibrillary acidic protein (GFAP) expression by immunohistochemisty and the ultrastructural changes of astrocytes in the hippocampus under an electron microscope. RESULTS: Immunohistochemical analysis showed the expression of GFAP in the HIBD groups with and without electric stimulation increased significantly compared with the control group on day 3, reached the peak on day 7, and the increased expression remained till to day 21. The GFAP expression in the electric stimulation group was significantly lower than that in the untreated HIBD group at all time points. Under the electron microscope, the astrocytes in the untreated HIBD group were swollen and the amount of organelles was reduced, while the swelling of astrocytes was alleviated and the organelles remained in integrity in the electric stimulation group. CONCLUSIONS: The electric stimulation at the cerebellar fastigial nucleus can inhibit the excessive proliferation of astrocytes and relieve the structural damage of astrocytes in neonatal rats following HIBD.