Protective effect of oxysophoridine on cerebral ischemia and reperfusion injury in mice

OBJECTIVE The purpose of this study was to obseve the protective effects of OSR(oxysophoridine,OSR) on cerebral ischemia and reperfusion injury in mice and to explore its possible protective mechanism.METHODS ICR mice were divided into a sham-operated group,a vehicle group,OSR(62.5,125,250 mg·kg-1) groups and a nimodipine(6 mg·kg-1) group.I.p.administration of OSR(62.5,125,250 mg·kg-1) in OSR groups for 7 d,ig administration of nimodipine(6 mg·kg-1) in nimodipine group for 7 d,ip administration of the same volume saline in sham-operated group and vehicle group for 7 d.Mice models of focal cerebral ischemia and reperfusion injury were established by occlusion of the right middle cerebral artery for 2 h followed by 24 h reperfusion except the sham-operated group.After 24 h of reperfusion,mice were tested for neurological deficit scores with the method of Bederson′s score,the cerebral infarct volume were assessed with the method of TTC staining in mice,the brain water content were determined by dry/wet weight method and the cerebral index were counted in mice,the levels of adenosine-triphosphate(ATP),maleic dialdehydle(MDA),glutathione peroxidase(GSH-PX),superoxide dismutase(SOD),catalase(CAT),nitric oxide(NO),nitric oxide synthase(NOS) and lactate dehydrogenase(LDH) in the brain tissues were measured with the method of spectrophotometry.RESULTS Compare to the model group,OSR(125,250 mg·kg-1) and nimodipine(6 mg·kg-1)reduced the neurological deficits scores(P<0.01) and the cerebral infarct volume(P<0.05).Compare to the model group,OSR(62.5,125,250 mg·kg-1) and nimodipine(6 mg·kg-1)reduced the brain water content(P<0.01).Compare to the model group,OSR(125,250 mgp·kg-1) and nimodipine(6 mg·kg-1)reduced the cerebral index(P<0.05).Compare to the model group,OSR(62.5,125,250 mg·kg-1) and nimodipine(6 mg·kg-1)reduced the contents of MDA,NO(P<0.01) and increased the contents of ATP(P<0.01).Compare to the model group,OSR(62.5,125,250 mg·kg-1) and nimodipine(6 mg·kg-1)enhanced the activities of SOD,GSH-PX,LDH and CAT(P<0.01),also decreased the activity of NOS(P<0.01).CONCLUSION OSR has significant protective effects of cerebral ischemia and reperfusion injury in mice,the effective mechanism of OSR might relate to the alleviation of oxidative stress.     

氧化槐定碱对小鼠急性脑缺血损伤的保护作用

目的:研究氧化槐定碱(Oxysophoridine,OSR)对小鼠脑组织急性缺血的保护作用。方法:ICR小鼠50只随机分为5组:对照组;OSR(62.51,25,250 mg/kg)组;尼莫地平(20mg/kg)组。各实验组分别灌胃7d,1次/d;对照组给予相同容积的生理盐水。末次给药后1小时,采用快速断头法制备小鼠急性全脑缺血模型。观察小鼠的喘息次数和喘息维持时间;取小鼠脑组织测定丙二醛(MDA)的含量和超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、乳酸脱氢酶(LDH)、肌酸激酶(CK)以及一氧化氮合酶(NOS)的活性。结果:与对照组比较,OSR(125、250mg/kg)组和尼莫地平(20mg/kg)组小鼠断头后喘息次数明显增加,喘息维持时间显著延长;与对照组比较,OSR(62.51、25、250mg/kg)组和尼莫地平(20mg/kg)组小鼠脑组织MDA含量明显降低;与对照组比较,OSR(1252、50mg/kg)组和尼莫地平(20mg/kg)组小鼠脑组织SOD、GSH-Px活性显著增高;与对照组比较,OSR(125、250mg/kg)组和尼莫地平(20mg/kg)组小鼠脑组织LDH、CK活性明显增高;与对照组比较,OSR(1252、50mg/kg)组和尼莫地平(20mg/kg)组小鼠脑组织NOS活性显著降低。结论:氧化槐定碱对小鼠急性脑缺血损伤有明显的保护作用,其作用机制可能与其抗氧化作用有关。     

苯-环己烷-正己烷三元系过量焓的研究

用自制的等温稀释型量热计测定了298.15K时苯 环己烷、苯 正己烷、正己烷 环己烷三对二元系和苯 环己烷 正己烷三元系的过量焓。根据Flory理论和UNIQUAC模型对所得二元系过量焓的数据进行关联,由关联所得的二元相互作用参数,预测了苯 环己烷 正己烷三元系的过量焓。结果良好。     

氧化槐定碱对新生大鼠海马神经元缺氧损伤的保护作用及其作用机制

目的:研究氧化槐定碱(oxysophoridine,OSR)对原代培养的新生大鼠海马神经元缺氧损伤的保护作用及其机制。方法:以原代培养的新生大鼠海马神经元为研究对象,用无糖培养液结合物理性缺氧建立缺氧损伤模型,测定神经细胞的存活率、乳酸脱氢酶(LDH)漏出率以及细胞中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、一氧化氮合酶(NOS)和一氧化氮(NO)水平的变化。采用荧光双波长分光光度计测定神经细胞内游离钙离子浓度([Ca2+]i)的变化。结果:缺氧损伤模型组能在短时间内造成神经元的死亡,LDH漏出率的增多,MDA,NO含量增多,NOS活性升高,SOD,GSH-PX活性降低,细胞内[Ca2+]i增加。OSR组(0.625,5,10μg.L-1)能不同程度地降低缺氧模型对神经元的损伤。结论:氧化槐定碱对新生大鼠海马神经元缺氧损伤具有明显的保护作用,其机制可能与减轻细胞内钙离子超载以及抗氧化损伤有关。     

氧化槐定碱对小鼠局灶性脑缺血再灌注损伤后NO、NOS变化的影响

目的探讨氧化槐定碱(Oxysophoridine,OSR)对小鼠脑缺血再灌注损伤的保护作用及其可能的作用机制。方法 ICR小鼠60只,随机分为6组:假手术组;模型组;OSR(62.5、125、250mg·kg-1)组;尼莫地平(6mg·kg-1)组。OSR组和尼莫地平组造模前预防性给药5d、缺血前1h及缺血再灌注后12h再分别给药1次。假手术组和模型组给予相同体积的生理盐水,各实验组除尼莫地平组灌胃,其他各组均腹腔注射。末次给药后1小时,采用线栓法构建小鼠大脑中动脉阻塞局灶性脑缺血再灌注损伤模型。采用Bederson的评分方法对小鼠神经功能缺陷进行评分;采用TTC染色法对小鼠进行脑梗死面积和脑梗死体积的检测;采用分光光度法测定小鼠脑缺血再灌注损伤侧脑组织一氧化氮(NO)含量及一氧化氮合成酶(NOS)活性。结果与模型组比较,OSR(125、250 mg·kg-1)组和尼莫地平组可明显降低小鼠神经功能缺陷评分(P<0.01);OSR(125、250 mg·kg-1)组和尼莫地平组可显著减少小鼠脑梗死体积(P<0.05,P<0.01);OSR(62.5、125、250mg·kg-1)组和尼莫地平组能明显降低小鼠脑缺血再灌注损伤侧脑组织NO含量(P<0.01);OSR(125、250 mg·kg-1)组和尼莫地平组能显著降低小鼠脑缺血再灌注损伤侧脑组织NOS活性(P<0.01)。结论OSR对脑缺血再灌注损伤小鼠有良好的保护作用,其作用机制可能与抗氧化应激有关。