硫辛酸对6-羟多巴胺诱导的帕金森模型大鼠的保护作用  

Neuroprotective Effect of Lipoic Acid on 6-OHDA-induced Rat Model of PD

作　　者：李成朋 韩飞[1,2] 杨梅[1,2] 魏操 周波[3] 张春林[3] 焦玲[4] 官志忠[1,2,5] 禹文峰[1,2] LI Chengpeng HAN Fei YANG Mei WEI Cao ZHOU Bo ZHANG Chunlin JIAO Ling GUAN Zhizhong YU Wenfeng(The Key Laboratory of Molecular Biology, Guizhou Medical University, Guiyang 550004, Guizhou, China The Education Ministry Key Laboratory of Endemic Diseases and Diseases of Ethenic Minority, Guizhou Medical University, Guiyang 550004, Guizhou, China Department of Biology, Guizhou Medical University, Guiyang 550004, Guizhou , China Department of Neurology of Affiliated Hospital, Guizhou Medical University, Guiyang 550004, Guizhou, China Department of Pathology, Guizhou Medical University, Guiyang 550004, Guizhou, China)

机构地区：[1]贵州医科大学分子生物学重点实验室,贵州贵阳550004 [2]贵州医科大学地方病与少数民族性疾病教育部重点实验室,贵州贵阳550004 [3]贵州医科大学生物教研室,贵州贵阳550004 [4]贵州医科大学附院神经内科,贵州贵阳550004 [5]贵州医科大学病理学教研室,贵州贵阳550004

出　　处：《贵州医科大学学报》2017年第3期249-252,共4页Journal of Guizhou Medical University

基　　金：国家自然科学基金(81360199);教育部科学技术研究项目(213032A);贵州省国际科技合作计划项目[黔科合外G字(2013)7026号];贵州省创新计划项目[黔教合协同创新中心(2014)06];贵州省教育厅项目(2015年贵州省普通高等学校地方病和少数民族疾病防控创新团队);贵州省科技厅计划课题[黔科合重大专项字(2014)6008]

摘　　要：目的:探讨硫辛酸(LA)对6-羟多巴胺(6-OHDA)诱导的帕金森病(PD)模型大鼠的神经保护功能。方法:健康雄性SD大鼠30只,随机分为假手术组、PD模型组和PD干预组,采用立体定位技术向PD模型组和PD干预组大鼠右侧大脑纹状体注射6-OHDA诱导建立PD大鼠模型,假手术组注射抗坏血酸的生理盐水;术后第4周开始,PD干预组腹腔连续注射LA 14 d,PD模型组和假手术组注射生理盐水;建模后第4周和第7周进行阿扑吗啡(APO)诱导的旋转行为学检测,建模后第4、5、6和7周通过圆筒实验测试大鼠左前肢的使用率;行为学检测结束后,免疫组化染色观察各组大鼠酪氨酸羟化酶(TH)阳性细胞表达。结果:注射APO后,PD模型组和PD干预组均出现向健侧旋转的行为,在第4周时旋转速度均≥3 r/min,表明PD大鼠复制成功;LA干预后(造模后第7周),PD干预组比PD模型组大鼠的旋转速度明显减慢,亦比本组干预前(第4周)减慢,差异具有统计学意义(P<0.05);与假手术组大鼠比较,造模后第5周开始,PD模型和PD干预大鼠的左前肢使用率减少(P<0.05),PD干预组大鼠左前肢的使用率比PD模型组增加(P<0.05);免疫组化示,PD干预组TH染色阳性细胞数较PD模型组多。结论:LA对6-OHDA诱导的PD模型大鼠的黑质多巴胺能神经元具有神经保护作用。Objective：To investigate the neuroprotective effect of lipoic acid（ LA） on 6-OHDA induced rat model of Parkinson disease（ PD）. Methods：30 healthy adult male Sprague-Dawley rats were randomly divided into sham operation group,PD model group and PD treatment group. The PD model and PD treatment groups received unilateral 6-OHDA injection into right corpus striatum with stereotactic technique to establish the animal model of PD. The sham operation group was injected saline. After 4 weeks of operation,the PD treatment group was continuously intraperitoneal injected with LA for 14 days. PD model group and sham operation group injected saline; after 4^th and 7^th week of modeling,APO induing Rotational behavior were tested,and Cylinder test changes of rats were observed after 4^th,5^th,6^th and 7^th week. Immunohistochemistry was used to detect the tyrosine hydroxylase（ TH） positive cell expression. Results：After APO injection,PD model group and PD treatment group showed rotation behavior to the healthy side,rotation speed were≥3 r/min in 4^th week,indicating PD rats duplicated successfully; after LA treatment（ 7^th week after modeling）,rotation speed of PD treatment group was obviously slower than PD model group,and also slower than itself in the 4^th week,differences were statistical significant（ P〈0. 05）; comparing with sham operation group rats,since the beginning of 5^th week,left fore limb usage of rats in PD model group and PD treatment group decreased（ P〈0. 05）; left fore limb usage of rats in PD treatment group increased more than PD model group（ P〈0. 05）; IHC indicated that TH positive apoptotic cells of PD treatment group were more than PD model group. Conclusions：LA has neuroprotective effects on the DA neurons in the 6-OHDA induced animal model of PD.

关 键 词：帕金森病 硫辛酸 6-羟多巴胺 氧化应激 多巴胺 酪氨酸羟化酶 

分 类 号：R322.81[医药卫生—人体解剖和组织胚胎学]