钙调激酶Ⅱ抑制剂对帕金森病运动并发症大鼠谷氨酸受体GluR1亚基特性的影响  

The research on the property of GIuR1 subunit in rat models of motor complication of Parkinson＇ s disease after CaMKII inhibitor KN-93 treatment

作　　者：巴茂文[1] 孔敏[2] 于国平[1] 孙旭文[1] 刘竹丽[1] 

机构地区：[1]烟台市毓璜顶医院神经内科,烟台254000 [2]烟台市烟台山医院神经内科

出　　处：《中华行为医学与脑科学杂志》2010年第10期888-890,共3页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：基金项目：烟台市科学技术发展计划项目（2008142-1）

摘　　要：目的 探讨钙调激酶Ⅱ抑制剂KN-93对帕金森病运动并发症大鼠行为学及GluR1831位丝氨酸磷酸化的影响.方法 将6-羟基多巴立体定向注射于大鼠前脑内侧束建立帕金森病动物模型.对模型成功的帕金森病大鼠接受每日2次左旋多巴（每公斤体质量50mg左旋多巴加每公斤体质量12.5 mg苄丝肼）腹腔注射,持续22d.在第23天左旋多巴注射前,帕金森病大鼠给予KN-93处理.评估旋转反应时间,采用蛋白印迹法及免疫组织化学检测纹状体区GluR1和GluR1831位丝氨酸磷酸化表达情况.结果 钙调激酶Ⅱ抑制剂KN-93逆转了左旋多巴所诱导的帕金森病大鼠旋转时间的缩短;此外,KN-93能调节与行为学改变密切相关的GluR1的亚细胞分布,且使GluR1831位丝氨酸磷酸化水平明显降低,其表达量分别为（83.4±4.2）%与（47.2±5.2）%.结论 钙调激酶Ⅱ可能通过介导GluRl的831位丝氨酸磷酸化参与了运动并发症的发生,抑制CaMKⅡ信号激酶的药物可能是治疗PD运动并发症的一种新的治疗方式.Objective To investigate the alteration of phosphorylated GluR1Ser831 and behavioural effects in a rat model of levodopa-induced motor complications after Ca2 ＋/calmodulin-dependent protein kinase Ⅱ （CaMKⅡ） inhibitor KN-93 treatment. Methods The hemi-parkinsonian rat model was produced by injecting stereotaxically 6-OHDA to right medial forebrain bundle. Then, rats were intraperitoneally treated with levodopa （ 50 mg/kg with benserazide 12.5 mg/kg,twice daily） for 22 days. On day 23 ,rats received KN-93 before levodopa administration. Rotational duration was estimated. After sacrificed, subcellualr distribution of GluR1 and phosphorylated GluR1Ser831 were observed by western blot. Results The study showed that CaMKⅡ inhibitor KN-93 prolonged rotational duration. Moreover, KN-93 could regulate subcellular distribution of GluR1 and reduce hyperphosphorylation of GluR1 Ser831, which was closely associated with levodopa-induced motor complications. The expression of membrane GluR1 and phosphorylated GluR1Ser831 was （83.4 ±4.2）% and （47.2 ±5.2）% ,respectively. Conclusions These results indicated that activation of CaMKⅡ contributed to development of motor complications, through a mechanism that involved an increase in phosphorylated GluR1 Ser831. Pharmaceuticals which act to inhibit CaMKⅡ may be useful in the treatment of the motor complications in parkinsonian patients.

关 键 词：帕金森病 运动并发症 谷氨酸受体 磷酸化 钙调激酶II 

分 类 号：R742.5[医药卫生—神经病学与精神病学]