艾滋病相关痴呆机制研究:鼠海马脑片 CA1区突触传递及可塑性与 HIV-1包膜糖蛋白 gp120的关系

背景目前对艾滋病相关性痴呆(HIV 1 associated dementia,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( human immunodeficiency virus I type, 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 [国家中医药管理局三级重点实验室(登记号TCM- 03- 131) ]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 (excitatorypostsynaptic potential,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 term potentiation, LTP)的影响. 结果发现 gp120对大鼠海马 CA1区 LTP产生抑制作用[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],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 [LTP的平均幅度为(198.8± 16.2)%, n=8, P< 0.01]. 结论 gp120可能是通过抑制海马 CA1区的 LTP而参与HAD的形成.

Mechanism study of acquired immunodeficiency syndrome associated dementia:the relationship between the synaptic transmission and plasticity of hippocampal CA1 area in rats and human immunodeficiency virus 1 enveloped protein gp120

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.