The effect of PARP inhibitor on the delayed development cerebral vasospasm after subarachnoid hemorrhage and inflammatory factors / 西安交通大学学报(医学版)

ABSTRACT

ABSTRACTObjective 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 groupsnormal 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.