辛伐他汀对谷氨酸损伤的大鼠海马组织中AMPA受体GluR2表达的影响  

Effect of Simvastatin on expression of GluR2 in the hippocampus of rats injured by Glutamate

作　　者：丁燕[1] 魏欣冰[1] 韩玉霞[1] 丁华[1] 

机构地区：[1]山东大学医学院药理学研究所,济南250012

出　　处：《山东大学学报（医学版）》2009年第5期38-41,45,共5页Journal of Shandong University:Health Sciences

摘　　要：目的研究辛伐他汀对谷氨酸损伤的大鼠海马组织中AMPA受体GluR2表达的影响。方法40只雄性Wistar大鼠随机分为假手术组、谷氨酸损伤组、辛伐他汀10 mg/kg组和20 mg/kg组。连续灌胃给药10 d后,麻醉状态下对大鼠行侧脑室注射,假手术组大鼠给予注射4μL生理盐水,其余组大鼠给予注射等体积谷氨酸溶液,2 h后,每组取5只大鼠,断头取脑,分离海马组织,采用RT-PCR方法观察大鼠海马组织中GluR2的mRNA表达情况;其余大鼠用多聚甲醛灌流后取出海马组织做病理切片,采用免疫组织化学方法观察其蛋白表达情况。结果与假手术组相比,谷氨酸损伤组大鼠海马组织中GluR2在mRNA和蛋白水平的表达均降低(P<0.01);辛伐他汀(10、20 mg/kg)组大鼠海马组织中GluR2的mRNA和蛋白水平的表达均明显升高。结论影响AMPA受体GluR2的表达可能是辛伐他汀抗谷氨酸损伤作用的机制之一。Objective To investigate the effect of Simvastatin on expression of GluR2 in the hippocampus of rats. Methods 40 male Wistar rats were randomly divided into 4 groups： the sham-operation group, the glutamate-induced injury group, the simvastatin 10 mg/kg and 20 mg/kg dose groups. Normal saline or Simvastatin solution were used for intra-gastric administration for 10 continuous days. Under an anesthesia state, rats in the sham-operation group were given 4 μL normal saline and those from other three groups were given 4 pL glutamate solution （ 1 mg/kg） through the lateral ventricle. The mRNA and protein expressions of GluR2 were determined 2 h after injection with glutamate solution by RT-PCR or immunochemistry. Result Compared with rats in the sham-operation group, both mRNA and protein expressions of GluR2 were decreased in the hippocampus of those in the glutamate-induced injury group （ P 〈 0.01）. Simvastatin （both 10 mg/kg and 20 mg/kg） can significantly decrease the reduction of GluR2 induced by injection of glutamate solution （P 〈 0.05, P 〈 0.01, respectively）. Conclusion Simvastatin can reduce or prevent glutamate-induced hippocampus injury, which may be mediated by enhancing expression of GluR2.

关 键 词：辛伐他汀 谷氨酸 受体 海马 大鼠 WISTAR 

分 类 号：R965[医药卫生—药理学]