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- 2016
PARP抑制剂对蛛网膜下腔出血后迟发型血管痉挛及炎症因子的影响
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Abstract:
摘要：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(30mg/kg)，于2次注血后3、5、7、14d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5d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。
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 (30mg/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 (16.44±1.32)μm and (178.21±11.13)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 [(402.16±48.99)ng/mL] were
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