多聚腺苷二磷酸核糖聚合酶抑制剂对脑缺血大鼠海马炎性因子表达水平影响.docVIP

多聚腺苷二磷酸核糖聚合酶抑制剂对脑缺血大鼠海马炎性因子表达水平影响 　　【摘要】 　　目的探讨多聚腺苷二磷酸核糖聚合酶(PARP)抑制剂3-氨基苯甲酰胺（3-AB）对脑缺血大鼠海马炎性因子表达水平的影响。方法56只大鼠随机分为假手术组、脑缺血对照组、3-AB组，用线栓法建立大鼠局灶性脑缺血模型，用免疫组化学染色法观察大鼠海马CA1区肿瘤坏死因子-a（TNF-a）和基质金属蛋白酶（MMP-9）的表达。结果与假手术组比较，缺血对照组及3-AB组的海马CA1区TNF-a和MMP-9的表达均明显增高(均P ＜0.01)；与脑缺血对照组比较，3-AB组海马CA1区TNF-a和MMP-9的表达均明显减少（P ＜0.05）。结论PARP抑制剂3-AB能明显降低脑缺血大鼠海马CA1区炎性因子TNF-a和MMP-9的表达水平，提示其有减轻炎症反应及神经保护作用。 　　【关键词】脑缺血；多聚腺苷二磷酸核糖聚合酶；3-氨基苯甲酰胺；肿瘤坏死因子-a；基质金属蛋白酶-9 　　The Protective Effect of PARP inhibitor on Cerebral Ischemia of Rats in Delayed Treatment 　　Zhang wei-fa, Wang dong-yu 　　【Abstract】Objective To explore the poly(ADP-ribose) polymerase(PARP) inhibitor 3-aminobenzamide(3-AB) on cerebral ischemia of rats in delayed treatment.MethodsThe rats were divided randomly into sham operation group,ischemica control group, 3-AB group.Rat model of cerebral ischemia was established by left middle cerebral artery occlusion(MCAO).At the different time points, killed the rats and brain tissues of rats were isolated. The expressions of TNF-a and MMP-9 in hippocampus CA1 region after MCAO were detected in immuno-histochemical methed.ResultsCompared with ischemia groups, the number of TNF-a and MMP-9 positive cell in 3-AB group were decreased significantly at the same time point（P0.05 or P0.01）. Conclusion Administration of PARP inhibitor 3-AB at 8 h after MCAO has a large brains protective effect.This effect may be mediated by decreased the expression of TNF-a and MMP-9 in hippocampus CA1 region of rats,suppression of the post -ischemic brain inflammatory response. 　　【Key words】 brain ischemia;poly(ADP-ribose) polymerase; inflammation;tnf-a;mmp-9 　　【中图分类号】R743.3 【文献标识码】B 【文章编号】1005-0515(2011)10-0016-03 　　 　　 　　缺血性脑血管病具有高发病率、高致残率及高死亡率等特点，近年来炎症反应在缺血性脑损伤中的作用受到广泛重视，脑组织的炎症反应主要特征是小胶质细胞的的激活，研究发现小胶质细胞的激活与多聚腺苷二磷酸核糖聚合酶(PARP)密切相关, PARP是核转录因子-kB (NF-kB)介导的小胶质细胞的基因转录、整合素的表达、形态改变、迁移和神经毒性所必需的因子，脑缺血后小胶质细胞的全部激活需要较长的时间，白细胞从外周血中浸润到脑组织需要更长的时间［1］。因此抑制PARP的活性在延长缺血性脑卒中治疗时间窗、减轻脑组织损伤等方面具有良好的应用前景，目前国内尚无与此有关的报道。本实验通过在大鼠大脑中动脉阻塞8