氧化槐定碱对小鼠脑缺血再灌注的脑组织中NMDA受体NR_1亚基表达的影响  

Effects of oxysophoridine on NMDA NR_1 expression in the brain tissue of mice with cerebral ischemia and reperfusion injury

作　　者：摆茹[1] 张快[2] 王洁 王腾飞[2] 郝银菊[2] 王淑静[4] 余建强[2] 

机构地区：[1]宁夏医科大学病原生物学与免疫学系,宁夏银川750004 [2]宁夏医科大学药理系,宁夏银川750004 [3]宁夏医学科学研究所,宁夏银川750004 [4]宁夏医科大学科学技术中心,宁夏银川750004

出　　处：《华西药学杂志》2013年第6期571-573,共3页West China Journal of Pharmaceutical Sciences

基　　金：宁夏自然科学基金(NZ11212);宁夏回族自治区高等学校科学技术研究项目(NGY2012055);宁夏回族自治区卫生厅重点科研计划课题(2012152)

摘　　要：目的探讨氧化槐定碱(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。方法将ICR小鼠60只随机分为假手术组、模型组、OSR(62.5、125、250 mg·kg-1)组、尼莫地平(6 mg·kg-1)组,OSR组和尼莫地平组造模前预防性给药5 d、缺血前1 h及缺血再灌注后12 h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外,其他各组均腹腔注射,末次给药后1 h,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。利用干湿重法测定小鼠脑缺血再灌注损伤侧脑组织的含水量,计算脑指数。利用实时定量RT-PCR、Western blot法检测小鼠脑缺血再灌注损伤侧脑组织皮层中NMDA受体NR1亚基mRNA和蛋白的表达。结果与模型组比较,OSR(62.5、125、250 mg·kg-1)组和尼莫地平组可明显降低小鼠脑缺血再灌注损伤侧脑组织的含水量(P<0.01);OSR(125、250 mg·kg-1)组和尼莫地平组可显著降低小鼠脑缺血再灌注损伤侧脑组织的脑指数(P<0.05,P<0.01)。与模型组比较,OSR(250 mg·kg-1)组和尼莫地平组能明显抑制小鼠脑缺血再灌注损伤侧脑组织皮层NMDA受体NR1亚基mRNA和蛋白的表达(P<0.01)。结论OSR对小鼠脑缺血再灌注损伤有良好的保护作用,其作用机制可能与抑制NMDA受体NR1亚基表达有关。OBJECTIVE To investigate the protective effects of oxysophoridine （OSR） on cerebral ischemia and reperfusion injury （CIRI） in mice and to explore its possible protective mechanism. METHODS The CIRI model of mice was induced with an 6/0 nylon monofilament coated with silicone hardener mixture via the internal carotid artery. Brain water content was determined by dry/wet weight method and the cerebral index was counted in mice. The expression of NMDA NRI mRNA and the expression of NMDA NR1 pro- tein were tested with the method of Real - time RT - PCR and Western blot in mice. RESULTS Compared with the model group, OSR （62.5,125,250 mg-kg-1 ） and nimodipine（6 mg.kg-j ） reduced the brain water content（ P 〈 0.01 ）. OSR（ 125,250 mg-kg-1 ） and nimodipine（6 mg. kg-1 ） reduced the cerebral index （ P 〈 0. 05, P 〈 0.01 ）. mRNA and protein expression of NMDA NRl were decreased by OSR （ 250 nag. kg - 1 ） and nimodipine （ 6 mg. kg - 1 ） （ p 〈 0.01 ）. CONCLUSION OSR has significantly protective effects of CIRI in mice,the effective mechanism of OSR might relate to inhibit the expression of NMDA NRi receptor.

关 键 词：氧化槐定碱 脑缺血再灌注损伤 NMDA NR1 小鼠 

分 类 号：R96[医药卫生—药理学]