胆碱酯酶抑制剂他克林对兔内毒素性脑损伤的影响

Effect of Cholinesterase Inhibitor on Endotoxin-induced Brain Injury in Rabbits

目的评价胆碱酯酶抑制剂他克林对兔内毒素性脑损伤的影响。方法健康成年雄性新西兰大白兔21只，体重1．7-2．3kg，采用随机数字表法，将其随机分为3组0=7）：假手术组（S组）脑池内注射生理盐水；内毒素组（LPS组）脑池内注射内毒素200ug／kg；胆碱酯酶抑制剂组（THA组）脑池内注射内毒素200μg／kg和盐酸他克林150μg／kg。注射后4h时处死动物，取脑组织，提取细胞核蛋白，采用Westernblot法测定NF-KBp65表达，ELISA法测定血浆、脑脊液和脑组织TNF-α水平，采用分光光度法测定脑组织髓过氧化物酶（MPO）活性，称重后计算湿干重比。结果与S组比较，LPS组和THA组NF-KBp65表达上调，血浆、脑脊液和脑组织TNF-α水平、MPO活性和湿干重比升高（P＜O．05）；与LPS组比较，THA组NF-KBp65表达下调，血浆、脑脊液和脑组织TNF-α水平、MPO活性和湿干重比降低（R＜O．05）。结论胆碱酯酶抑制剂他克林可通过抑制局部炎性反应减轻兔内毒素性脑损伤。

Objective To investigate the effect of cholinesterase inhibitor on endotoxin-induced brain injury in rabbits. Methods Twenty- one healthy male rabbits were randomly assigned into three groups （ n = 7 each）： group sham operation （group S）, lipopolysaccharide （LPS） group and cholinesterase inhibitor （tacrine hydrochloride, THA） group. LPS 200μg/kg was intracerebroventricularly injected in LPS group, LPS 200μg/ kg and tacrine hydrochloride 150 μg/kg were injected in THA group, while same volume of normal saline was injected in S group. Then blood and tissue samples were collected in different groups after 4 hours. Nuclear factor-kappa B （NF-kB） p65 activity of brain tissues was determined by using Western blot analysis. Tumor necrosis factor-alpha （TNF- a ） levels in plasma, cerebrospinal fluid and brain tissues were measured using enzyme linked immunosorbent assay. The brain tissue＇s myeloperoxidase （MPO） activity and the ratio of wet to dry weight （W/D） were also analyzed. Results As compared with S group, TNF- a level in plasma, cerebrospinal fluid and brain tissues, NF-KB p65 level, MPO activity and W/D ratio increased in LPS and THA groups （P 〈 0.05）. When compared with LPS group, TNF- a level in plasma, cerebrospinal fluid and brain tissues, NF-KB p65 level, MPO activity and W/D ratio decreased in THA group （ P 〈 0.05 ）. Conclusion Cholinesterase inhibitor can attenuate the endotoxin-induced brain injury through inhibiting local inflammatory responses.