李成朋,韩飞,杨梅,魏操,周波,张春林,焦玲,官志忠,禹文峰
LI Chengpeng,HAN Fei,YANG Mei,WEI Cao,ZHOU Bo,ZHANG Chunlin,JIAO Ling,GUAN Zhizhong,YU Wenfeng

• 1:贵州医科大学分子生物学重点实验室
• 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
• 3:贵州医科大学生物教研室
• 4:贵州医科大学附院神经内科

摘要(Abstract)：

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 5thweek,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(KeyWords)： 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
Parkinson's disease;lipoic acid;6-hydroxydopamine;oxidative stress;dopmine;tyrosine hydroxylase

Abstract:

Keywords:

基金项目(Foundation): 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]

作者(Author): 李成朋,韩飞,杨梅,魏操,周波,张春林,焦玲,官志忠,禹文峰
LI Chengpeng,HAN Fei,YANG Mei,WEI Cao,ZHOU Bo,ZHANG Chunlin,JIAO Ling,GUAN Zhizhong,YU Wenfeng

DOI: 10.19367/j.cnki.1000-2707.2017.03.001

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