新生大鼠脑白质损伤时神经胶质细胞凋亡与iNOS的表达

Expression of iNOS protein and gliacyte apoptosis in neonatal rats with white matter damage

摘要:

目的：诱导型一氧化氮合酶(iNOS) 是缺氧缺血（HI）后引起一氧化氮过量产生的主要限速酶，该研究通过观察HI后神经胶质细胞凋亡及iNOS表达的变化，探讨新生大鼠脑白质损伤(WMD)的发病机制。方法：将112只2日龄未成熟大鼠随机分为WMD组和假手术 (对照) 组，建立新生大鼠WMD模型，分别于HI后1 h、3 h、6 h、12 h、1 d、3 d及7 d处死，采用免疫组织化学法检测脑组织iNOS的表达，TUNEL法测定胶质细胞凋亡。结果：与对照组比较，WMD组iNOS于HI后1 h表达开始上升，1 d达到高峰；神经胶质细胞凋亡于HI后1 h显著增多，在HI后1 d达到高峰。结论：WMD新生大鼠中iNOS的表达显著增高可能导致神经胶质细胞的凋亡，参与HI后WMD的病理生理过程。

Abstract:

OBJECTIVE: Inducible nitric oxide synthase (iNOS) is a main rate-limiting enzyme resulting in over-production of nitric oxide following hypoxia-ischemia (HI). The aim of this study was to observe the expression of iNOS protein and gliacyte apoptosis in the brains of premature rats after HI, in order to explore possible relationships of iNOS with white matter damage (WMD). METHODS: One hundred and twelve 2-day-old premature rats were randomly subjected to right carotid ligation followed by 4 hrs hypoxic stress (WMD group) or sham operation (control group). The pups were sacrificed at 1, 3, 6, 12 hrs, and 1, 3 and 7 days after HI. Immunohistochemical technique was applied to determine the iNOS expression in periventricular white matter tissues. Gliacyte apoptosis was detected in these tissues by TUNEL. RESULTS: Compared with the control group, iNOS expression began to increase 1 hr after HI and reached the peak 1 day after HI in the WMD group. Gliacyte apoptosis increased 1 hr after HI and peaked 1 day after HI in the WMD group compared with the control group. CONCLUSIONS: In the neonatal rats with WMD, the expression of iNOS may be involved in the ischemic cellular events including apoptosis, and plays a role in the pathophysiological process of WMD.