中文摘要：

目的 探讨聚腺苷二磷酸核糖聚合酶（PARP）抑制剂PJ34对小鼠创伤性颅脑损伤（TBI）的保护作用.方法 将BALB/c雄性小鼠分为假手术组、模型组和PJ34组,建立小鼠可控性皮质打击伤（CCI）模型.分别在打击后6h、24h从运动、感觉、反射和平衡等方面评价小鼠的神经功能缺损程度,并测定脑挫裂伤体积.打击后24h时通过HE染色评价受损脑区神经元的损伤.分别在打击后6h、24h采用髓过氧化物酶（MPO）活性测定试剂盒测定损伤脑组织内MPO的活性;并采用Western blot方法分别检测细胞质和细胞核NF-κB p65亚单位的含量以及细胞质内炎性反应因子TNF-α和IL-1β的含量.结果 PJ34组打击后6h、24h神经功能评分分别为（8.20 ±0.25）分和（7.80±0.25）分,均低于模型组（12.40±0.38）分和（11.70±0.22）分（均P＜0.01）;脑挫裂伤体积分别为（10.25 ±0.61） mm3和（11.55±1.16） mm3,均小于模型组（25.07±1.45） mm3和（27.24±1.51） mm3（均P＜0.01）;MPO活性分别为（0.013 ±0.001） U/g和（0.018-±0.001） U/g,均低于模型组（0.024 ±0.001） U/g和（0.023 ±0.001） U/g（均P ＜0.05）;细胞质内NF-κB的表达水平均低于模型组（均P＜0.05）.PJ34组打击后24h细胞核内NF-κB的表达水平低于模型组（P＜0.01）,而6h细胞核内NF-κB水平与模型组之间的差异无统计学意义.PJ34组打击后6h和24h的TNF-α及IL-1β的表达水平均低于模型组,差异均有统计学意义（P＜0.05或P＜0.01）.结论 PARP-NF-κB炎性反应通路在TBI后的继发性损伤中起重要作用,PJ34可以阻断该通路,抑制TBI后的炎性反应,从而起到脑保护的作用.

英文摘要：

Objective To investigate whether PARP inhibitor,PJ34,participates in the inflammation related to PARP-NF-κB pathway in a mouse model of controlled cortical impact （CCI）.Methods One hundred and thirty-six BALB/c male mice were divided into 3 groups：sham-operated group,vehicle-treated group and PJ34-treated group.Injury to the cerebral cortex was produced with controlled cortical impact.Evaluation of the neurological deficits was performed at 6 h and 24 h after CCI,which included the motor,sensory,reflex testing and beam balance testing.The contusion volumes were measured after HE staining at 6 h and 24 h after CCI.The activities of MPO in contusion cortex were examined by using MPO ELISA kit.Western blot was performed to detect the levels of NF-κB p65 in cytosolic and nuclear fractions and to detect TNF-α and IL-1β in cytosolic fractions.Results Neurological severity scores at 6 h and 24 h after CCI in PJ34-treated group（8.20 ±0.25 and 7.80 ±0.25,respectively） are less than those in vehicle-treated group（12.40 ±0.38 and 11.70 ±0.22,respectively） （all P 〈0.01）.The contusion volume at 6 h and 24 h after CCI in PJ34-treated group[（10.25 ± 0.61） mm3 and （11.55 ±1.16） mm3,respectively] is less than that in vehicle-treated group[（25.07 ± 1.45）mm3 and （27.24 ± 1.51）mm3,respectively] （all P 〈 0.01）.The activities of MPO at 6 h and 24 h after CCI in PJ34-treated group [（0.013 ±0.001） U/g and （0.018 ± 0.001） U/g,respectively] is less than those in vehicle-treated group [（0.024 ± 0.001） U/g and （0.023 ± 0.001） U/g,respectively] （all P 〈 0.05）.Moreover,the expression level of NF-κB p65 in cytoplasm at 6 h and 24 h after CCI in PJ34-treated group is less than that in vehicle-treated group （all P 〈 0.05）.Compared with vehicle-treated group,the expression level of NF-κB p65 in cell nuclei at 24 h after CCI in PJ34-treated group is higher （P 〈0.01）.There is no significant difference between the expression level of NF-κB p65 in cell nucl