ABSTRACT:Objective To investigate the effects of poly ADP-ribose polymerase (PARP ) inhibitor 3-aminobenzene (3-AB)on the delayed development cerebral vasospasm (DCVS)after subarachnoid hemorrhage (SAH)and on the inflammatory factors,namely monocyte chemotactic protein 1 (MCP-1 )and hypersensitive c-reactive protein (hsCRP),and to explore the relationship between these and the signaling pathway of NF-kappa B (NF-κB).Methods Eighty male Sprague-Dawley rats were randomly divided into four groups:normal group (n =8),sham-operation group (n =8),SAH model group (n =32)and 3-AB group (n =32).We established 64 SAH model animals by double injection of blood into the cisterna magna.Half of the SAH model animals were treated with 3-AB by intraperitoneal injection (30 mg/kg).These rats were killed to obtain specimens respectively at days 3, 5,7 and 14 after the second blood injection.The morphological changes of basilar arteries were observed under the light microscope.The contents of PARP,MCP-1 and hsCRP in brain tissues were detected with enzyme-linked immunosorbent assay (ELISA).The expression of NF-κB in basilar arteries was determined by immunohistochemistry. Results Compared with those in the sham-operation group,the degree of basilar artery spasm reached the peak [(30.47±3.89)%]at day 5 after established SAH model;the thickness and diameter of basilar artery were (1 6.44 ±1.32)μm and (1 78.21 ± 1 1.13)μm,respectively.Cerebral blood flow was reduced by nearly 60% (P <0.01 ). The expression of NF-κB in the cytoplasm and nucleus and PARP content in brain tissue were both increased significantly (P < 0.01 ).MCP-1 [(365.29 ± 28.08 )pg/mL ] and hsCRP [(402.1 6 ± 48.99 )ng/mL ] were significantly enhanced (P <0.01).Compared with the SAH group,after 5 days’intervention with 3-AB,there was obvious alleviation in the spasm degree of basilar artery [(22.65±3.21)%],the thickness [(14.89±1.27)μm]and diameter [(1 98.56±10.91)μm],respectively (P <0.01).Cerebral blood flow was significantly enhanced,but the expression of NF-κB in the cytoplasm and nucleus was decreased and PARP in brain tissue was significantly decreased (P < 0.01 ).MCP-1 [(126.5 1 ± 18.67 )pg/mL]and hsCRP [(285.39 ± 39.07 )ng/mL]in brain tissue were significantly declined,respectively (P <0.01).Conclusion PARP inhibitor 3-AB can alleviate DCVS and inhibit the inflammatory response in brain tissue after SAH.The mechanism may be related to NF-κB signaling pathway.%目的：研究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)对大鼠蛛网膜下腔出血(SAH)后迟发型脑血管痉挛(DCVS)的作用及对炎症因子单核细胞趋化蛋白-1(MCP-1)、超敏 C 反应蛋白(hsCRP)含量的影响,并探讨其与 NF-κB 信号通路的关系。方法将80只 SD 大鼠随机分为正常对照组(n=8)、假手术组(n=8)、SAH组(n=32)和3-AB(n=32)组。采用枕大池2次注血法建立大鼠 SAH 模型,并给与大鼠腹腔注射3-AB(30 mg/kg),于2次注血后3、5、7、14 d 处死取材,光镜下观察 SAH 后脑基底动脉形态变化；ELISA 检测脑组织中 PARP 和MCP-1、hsCRP 的含量；免疫组化方法检测大鼠脑基底动脉 NF-κB 的表达。结果与假手术组比较,SAH 模型建立后第5天,大鼠基底动脉痉挛程度达到峰值[(30.47±3.89)%],基底动脉管壁厚度和管腔内径分别为(16.44±1.32)μm和(178.21±11.13)μm,脑血流量减少近60%(P <0.01),基底动脉 NF-κB 在胞质及核内表达明显增强,脑组织中PARP 含量显著升高(P <0.01),MCP-1、hsCRP 含量亦显著增高(P <0.01),分别为(365.29±28.08)pg/mL 和(402.16±48.99)ng/mL；与 SAH 组比较,3-AB 干预5 d 后,大鼠基底动脉痉挛程度、管腔狭窄、管壁增厚明显缓解(P <0.01),其值分别为(22.65±3.21)%、(14.89±1.27)μm 和(198.56±10.91)μm,脑血流量明显增加,基底动脉NF-κB 在胞质及核内表达明显降低,脑组织中 PARP 的含量显著降低(P <0.01),脑组织 MCP-1、hsCRP 含量显著下降(P <0.01),分别为(126.51±18.67)pg/mL 和(285.39±39.07)ng/mL。结论 PARP 抑制剂3-AB 能够减轻SAH 后迟发性脑血管痉挛,抑制脑组织的炎症反应,其机制可能与 NF-κB 信号通路有关。
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