28烷醇对6-羟基多巴胺致帕金森病大鼠的行为学作用及其机制研究  

Effects of Octacosanol on Behavioral Impairments and Its Mechanism through Nerve Growth Factor Mediated Pathway in Parkinsonism Rats Induced with 6-hydroxydopamine

作　　者：王涛[1] 乔洪文[1] 刘雁勇[2] 杨楠[2] 纪超[2] 陈彪[1] 左萍萍[2] 

机构地区：[1]首都医科大学宣武医院神经生物学研究室,北京市100053 [2]中国医学科学院基础医学研究所药理室,北京市100730

出　　处：《中国康复理论与实践》2013年第11期1001-1005,共5页Chinese Journal of Rehabilitation Theory and Practice

基　　金：国家973基金项目(No.2010CB934002;No.2011CB504101;No.2011CBA00408);国家自然科学基金资助项目(No.81050025);神经变性病教育部重点实验室开放课题(No.2012SJBX01);北京市脑重大疾病重点实验室开放课题(No.2013NZDJ05)

摘　　要：目的观察28烷醇对帕金森病模型大鼠的行为学改善作用与中脑水平神经生长因子(NGF)、神经生长因子前体(proNGF)及其各自受体表达的变化。方法将6-羟基多巴胺(6-OHDA)通过立体定位仪注入大鼠右侧纹状体,以28烷醇17.5 mg/kg(低剂量组)、35 mg/kg(中剂量组)、70 mg/kg(高剂量组)进行干预。给药2周后行阿朴吗啡诱导的旋转测试和平衡杆测试;TUNEL染色检测纹状体内的细胞凋亡情况;Western印迹法检测caspase-3、NGF及其受体、proNGF及其受体蛋白表达情况。结果与模型组相比,中剂量和高剂量组旋转试验和平衡杆实验成绩改善(P<0.05);高剂量组纹状体内凋亡小体减少(P<0.05),NGF及其受体TrkA表达增高(P<0.05),proNGF及其受体sortilin和p75NTR表达降低(P<0.05),caspase-3表达减少(P<0.05)。结论 28烷醇可改善帕金森病大鼠病理行为。其神经保护机制可能是调节NGF介导的细胞存活通路和proNGF介导的凋亡通路相关蛋白表达,进而减少神经细胞凋亡。Objective To investigate the effects of octacosanol on the behavioral changes and its potential mechanism in 6-hydroxydopa-mine-induced Parkinsonism rats. Methods 6-hydroxydopamine-induced Parkinsonism rats accepted octacosanol orally in the dosage of 17.5 mg/kg （low dose）, 35 mg/kg （medium dose） and 70 mg/kg （high dose） for 2 weeks, and then assessed with rotating test and narrow beam test. The apoptosis cells were counted with TUNEL assay, and the expression of nerve growth factor （NGF）, precursor of nerve growth fac-tor （proNGF）, as well as their receptors were detected with Western blotting. Results The achievement of behavioral tests significantly im-proved after administration of octacosanol （P〈0.05）, with the decrease of the apoptotic cells, more expression of NGF and its receptors TrkA, and less expression of caspase-3, proNGF and its receptors p75NTR and sortilin, especially at the dosage of 70 mg/kg （P〈0.05）. Con-clusion Octacosanol may protect the neurol impairment from 6-hydroxydopamine through NGF mediated pathway to decrease the apoptosis.

关 键 词：帕金森病 神经生长因子 神经生长因子前体 神经保护 凋亡 大鼠 

分 类 号：R742.5[医药卫生—神经病学与精神病学]