纳洛酮干预对大鼠脑出血后血肿周围神经细胞中氧化还原因子-1表达与凋亡的影响

Effects of naloxone on expression of Ref-1 and neuronal apoptosis after intracerebral hemorrhage in rats

目的 :观察盐酸纳洛酮对脑出血后血肿周围神经细胞中氧化还原因子 1(redoxfactor 1Ref 1)表达的影响。方法 :应用立体定向技术 ,将SD大鼠自体不凝血 5 0 μl 注入其尾状核区制备脑出血模型 ,将动物随机分为正常对照组 ,假手术组、出血组和纳洛酮干预组 ,并分别在不同时间点断头取脑 ,连续切片作Ref 1和TUNEL (terminaldeoxynucleotidyltrans ferase [TdT ] mediateddeoxyuridinetriphosphate[dUTP] biotinnickendlabeling)免疫组化染色。结果 :经盐酸纳洛酮干预后 ,血肿周围神经细胞中Ref 1表达与脑出血相对应组比较 ,在 12h影响不明显 ,4 8h能增加Ref 1表达 (P <0 .0 1) ;72h亦能增加Ref 1表达 (P <0 .0 5 ) ;盐酸纳洛酮干预性治疗后 ,血肿周围神经细胞中TUNEL阳性细胞数与脑出血相对应组比较 ,在 12h明显影响 ,4 8h能明显减少凋亡 (P <0 .0 5 ) ;72h更明显 (P <0 .0 1)。结论 :盐酸纳洛酮能通过提高ICH缺血半暗带区Ref 1表达等途径 ,增加修复氧化损伤的DNA能力 ,减少细胞凋亡 。

AIM: To observe the effects of naloxone on expression of Ref-1 and neuronal apoptosis in rat brain tissue around the caudate nucleus (damaged areas) after experimental intracerebral hemorrhage (ICH). METHODS: ICH was induced in rats using stereotactic infusion autologous blood 50 μl into the caudate nucleus. The male animals were randomly divided into normal control group, sham operation group,hemorrhage group and naloxone treatment group. The hemorrhage group and naloxone treatment group were divided into three different time point groups. TUNEL method was used to detect apoptosis, and immunohistochemitry method to detect expression of Ref-1 in cerebral tissues at different times. RESULTS: The quantity of the expression of Ref-1 within 72 h after ICH was significantly ascended (P< 0.05) and the quantity of TUNEL-positive cells within 72 h after ICH was significantly reduced (P< 0.01) by treatment with naloxone. CONCLUSION: Naloxone can increase the expression of Ref-1 and the ability of modifying DNA damaged by oxidize, and decrease apoptosis after ICH.