蛋白酶激活受体-1在高压氧预处理诱导大鼠脑出血后脑保护中的作用

Effects of Protease-activated Receptor-1(PAR-1)on Brain Tolerance after Experimental Intracerebral Hemorrhage Induced by Hyperbaric Oxygen Preconditioning

目的探讨蛋白酶激活受体-1(PAR-1)在高压氧预处理(HBOP)诱导的大鼠脑出血后神经保护中的作用。方法 (1)SD大鼠接受连续5次HBOP或假预处理(SP),预处理结束24h后,建立基底节区脑出血模型,72h后处死,观察脑水含量,神经功能评分,TUNEL法检测血肿周围神经细胞凋亡,免疫组化方法检测血肿周围组织PAR-1的表达。(2)SD大鼠HBOP预处理前基底节区给予PAR-1激动剂(PAR-AP)或生理盐水,接受连续5次HBOP,预处理结束24h后,建立基底节区脑出血模型,72h后处死,观察脑水含量、神经功能评分,血肿周围神经细胞凋亡和PAR-1的表达。结果高压氧预处理减轻大鼠脑出血后72h血肿周围脑组织水肿[(81.4±0.8)%vs(80.2±0.6)%,P<0.01],改善神经功能评分,减少血肿周围神经细胞凋亡,HBOP降低了血肿周围组织PAR-1的表达(P<0.05)。HBOP前给予PARAP激活PAR-1受体,消除了HBOP诱导的神经保护作用。结论高压氧预处理通过减轻脑组织水肿,减少神经细胞凋亡起到神经保护作用,下调PAR-1的表达是可能的作用机制之一。

Objective To investigate the effects of protease-activated receptor-1（PAR-1） on brain tolerance after experimental intrac-erebral hemorrhage induced by hyperbaric oxygen preconditioning. Methods This study had two experimental groups. Group 1 , Sprague-Dawley rats received five consecutive sessions of hyperbaric oxygen preconditioning （HBOP） or sham preconditioning （SP）.Twenty-four hours after preconditioning ,rats received an infusion of autologous blood into the caudate.They were killed 72 hours later ,and brain water content ,neurological function ,neuronal cell apoptosis and PAR-1 expression were measured. Group 2 ,rats re-ceived an intracaudate injection of PAR-1 agonist peptide （PAR-AP） or normal saline before HBOP ,then they received five consecu-tive sessions of HOBP.Twenty-four hours after HOBP ,rats received an intracaudate blood infusion.Brain water content ,neurological function ,neuronal cell apoptosis and PAR-1 expression were measured 72 hours after the rats were killed. Results HOBP reduced perihematomal edema 72 hours after ICH （（81.4 ± 0.8）% vs （80.2 ± 0.6）% ,P〈0.01） ,reduced neurological deficits and de-creased perihematoma neuronal cell apoptosis and improved PAR-1 expression（ P〈0.05）.Intracaudate infusion of PAR-AP activated PAR-1 expression and abolished HBOP induced neuro-protection.Conclusions HOBP attenuates brain edema formation ,neuronal cell apoptosis and neurological deficits after ICH.Inhibition of PAR-1 contributes to that effects.