盐酸苯环壬酯及其异构体抗NMDA神经毒性保护作用的比较  

Comparative protective effects of phencynonate hydrochloride and its optical isomers on NMDA-induced neurotoxicity

作　　者：任振宇[1] 彭双清[1] 仲伯华[1] 刘河[1] 刘克良[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《毒理学杂志》2007年第4期251-254,共4页Journal of Toxicology

基　　金：国家自然基金重大课题资助项目(203900508)

摘　　要：目的观察并比较盐酸苯环壬酯消旋体(phencynonate hydrochloride,PCH)及其不同旋光异构体——R(-)-PCH和S(+)-PCH对NMDA(N-甲基-D-天冬氨酸)神经毒性的保护作用。方法通过建立NMDA小鼠致死模型及PC12细胞损伤模型,测定PCH不同旋光异构体对小鼠存活率、细胞存活率及乳酸脱氢酶(lactate dehydrogenase,LDH)漏出的影响。结果PCH不同旋光异构体在体内体外均能对抗NMDA的神经毒性作用。R(-)-PCH在6mg/kg时发挥最大保护效应,使小鼠存活率提高到55.6%,保护效应优于S(+)-PCH;PCH消旋体的最佳保护效应与R(-)-PCH相当,但所需剂量高于R(-)-PCH。3mmol/L NMDA作用24h使细胞存活率降至对照组的63.5%,LDH漏出增加到对照组的2倍,5μmol/L R(-)-PCH作用使细胞存活率提高到对照组的80.5%(P<0.05,与对照组相比)并有效抑制NMDA所致的细胞LDH漏出;S(+)-PCH对细胞存活率无明显影响,但可以有效抑制LDH的漏出;PCH消旋体的作用介于二者之间,也发挥出显著性保护作用。结论PCH不同旋光异构体均可对抗NMDA神经毒性,R(-)-PCH的保护效应优于S(-)-PCH,是优性异构体,PCH消旋体的作用介于2个异构体之间。Objective To compare the neuroprotective effects of phencynonate hydrochloride （PCH） and its optical isomers on N-methy-D-aspirate（NMDA）induced neurotoxicity ,Methods A model of NMDA-induced lethality in mice and another model of NMDAinduced toxicity in PC12 cells were developed, and the protective effects of PCH racemate and its isomers were detected.Results PCH racemate and its isomers are effective in attenuating NMDA-induced toxicity both in vivo and in vitro. Pretreatment mice with 6 mg/kg R （-）-PCH promoted the survival rate up to 55.6%, more potent than 22.2% of S（ ＋ ）-PCH pretreatment group at the same dose.5 ,o.mol/L R（-）-PCH effectively increased PC12 cell viability and attenuated Lactate dehydregenase（LDH） release, while S（ ＋ ）-PCH was less effective. PCH racemate demonstrated a modest protection between its two isomers. Conclusion PCH racemate and its isomers all provide protection against NMDA-induced toxicity, and the protective effects R（-）-PCH are more potent than that of S（ ＋ ）-PCH both in vivo and in vitro.

关 键 词：NMDA 神经毒性 神经保护作用 旋光异构体 

分 类 号：R994[医药卫生—毒理学]