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

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20mg/kg组。连续灌胃给药10d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，2h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、20mg/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。

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

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 10mg/kg and 20mg/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 4μL normal saline and those from other three groups were given 4μL glutamate solution (1mg/kg) through the lateral ventricle. The mRNA and protein expressions of GluR2 were determined 2h after injection with glutamate solution by RT-PCR or immuno chemistry.  Result  Compared with rats in the sham-operation group, both mRNA andprotein expressions of GluR2 were decreased in the hippocampus of those in the glutamate-induced injury group (P＜0.01). Simvastatin (both 10mg/kg and 20mg/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.