摘要
背景:目前对艾滋病相关性痴呆(HIV-1associateddementia,HAD)仍没有特效的治疗药物,主要因为对HIV-1感染引起的神经损伤和坏死的机制,仍没有完全阐明。目的:探讨人类免疫缺陷病毒I型(humanimmunodeficiencyvirusItype,HIV-1)包膜糖蛋白gp120对鼠海马脑片CA1区的突触传递及可塑性的影响,以期阐明HAD的形成机制。设计:配对设计。单位:暨南大学医学院的病理生理教研室。材料:实验于2003-01/10在暨南大学医学院病理生理教研室犤国家中医药管理局三级重点实验室(登记号:TCM-03-131)犦完成。实验用2～5周龄雄性SD大鼠。干预:应用离体脑片灌流及记录技术。主要观察指标:记录大鼠海马CA1区的兴奋性突触后电位(excitatorypostsynapticpotential,EPSP),研究了gp120对高频电刺激Schaffer侧支引起的鼠长时程增强效应(long-termpotentiation,LTP)的影响。结果:发现gp120对大鼠海马CA1区LTP产生抑制作用犤LTP的平均幅度由正常的(216.1±14.0)%降到(90.8±6.0)%,n=12,P<0.01犦,对其基础EPSP没有影响。PKA/PKC蛋白激酶抑制剂H7可以反转这种抑制效应犤LTP的平均幅度为(198.8±16.2)%,n=8,P<0.01犦。结论:gp120可能是通过抑制海马CA1区的LTP而参与HAD的形成。
BACKGROUND:No particularly effective medicine could treat human immunodeficiency virus 1(HIV 1) associated dementia(HAD) at present,which mainly because the mechanism of HIV 1 infection induced neural damage and necrosis is still not completely clarified. OBJECTIVE:To investigate the effects of human immunodeficiency virus I type(HIV 1) enveloped protein(EP) gp120 on the synaptic transmission and plasticity in hippocampal CA1 area of rat to clarify the mechanism of HAD generation.DESIGN:A paired design.SETTING:Department of Pathophysiology of Medical College of Jinan University.MATERIALS:The study was conducted in the Department of Pathophysiology(a tertiary national key laboratory of National Administration for Traditional Chinese Medicine,registration number: TCM 03 131) of the Medical College of Jinan University from January to October of 2003.Male SD rats aged between 2 and 5 weeks were used in the study.INTERVENTIONS:Brain slice perfusion and recording technique was employed.MAIN OUTCOME MEASURES:To record the excitatory postsynaptic potential(EPSP) in hippocampal CA1 area in rat;to investigate the effects of gp120 on long term potentiation(LTP) induced by high frequency electric stimulation in Schaffer lateral branch.RESULTS:gp120 had inhibitive effect on LTP in hippocampal CA1 area in rat [the average amplitude of LTP decreased from normal (216.1±14.0) %to(90.8±6.0) %,n=12,P< 0.01],but had no effect on basic EPSP.PKA/PKC protein kinase(PK) inhibitor H7 could reverse this inhibitive effect [the average amplitude of LTP was(198.8±16.2) %,n=8,P< 0.01].CONCLUSION:gp120 might participate the generation of HAD through inhibiting LTP in hippocampal CA1 area.
出处
《中国临床康复》
CSCD
北大核心
2005年第4期213-215,共3页
Chinese Journal of Clinical Rehabilitation
基金
广东省医学科研基金项目(A2004327)
广东省自然科学基金项目(04010443)
广东省自然科学基金团队项目(039213)~~
