鼠尾草酸对MPTP诱导的多巴胺神经元损伤的保护作用研究  

Study on the protective effect of carnosic acid on MPTP-induced dopamine neuron damage

作　　者：李媛 耿艺娟 于浩飞 孙梦桢 张兰春 张荣平 胡炜彦 LI Yuan;GENG Yi-juan;YU Hao-fei;SUN Meng-zhen;ZHANG Lan-chun;ZHANG Rong-ping;HU Wei-yan(School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products,Kunming Medical University;School of Traditional Chinese Medicine,Yunnan University of TCM,Kunming 650500,China)

机构地区：[1]昆明医科大学药学院暨云南省天然药物药理重点实验室 [2]云南中医药大学中药学院,昆明650500

出　　处：《天然产物研究与开发》2021年第7期1172-1177,共6页Natural Product Research and Development

基　　金：国家自然科学基金地区基金(81960666);云南省创新团队(202005AE160004)。

摘　　要：探讨鼠尾草酸(carnosic acid,CA)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)诱导的多巴胺神经元损伤的保护作用。通过体外培养小鼠多巴胺能神经元,分为对照组(试剂空白组)、模型组(MPTP处理组)、药物组(高、中、低剂量CA处理组)和阳性对照组。采用细胞活性检测试剂盒(CCK-8)检测神经元活力;用酪氨酸羟化酶(tyrosine hydroxylase,TH)抗体进行免疫荧光染色,共聚焦显微镜下观察细胞形态;生化法检测乳酸脱氢酶(LDH)释放量和丙二醛(MDA)及超氧化物歧化酶(SOD)的活性;实时荧光聚合酶链式反应(RT-PCR)检测神经元凋亡相关基因caspase 3 mRNA的表达;免疫蛋白印迹(Western blot,WB)检测总caspase-3和剪切型caspase-3的表达。结果显示,与模型组比较,中、高浓度CA处理组神经元活力明显增强,神经元形态良好,培养液中LDH漏出减少、胞内MDA的生成减少,SOD活性增强,caspase-3 mRNA蛋白的表达显著下调。CA预处理对MPTP诱导的多巴胺神经元损伤具有保护作用,其机制可能与抑制神经元氧化损伤,阻止caspase-3异常升高有关。Oxidative stress-induced dopaminergic neurons toxicity is a key pathogenic factor of Parkinson’s disease.Protecting dopaminergic neurons from oxidants induced damage is beneficial to the treatment of PD.Carnosic acid(CA)has been reported to exhibit excellent anti-oxidative activity.In the present study,we investigated the protective effect of CA on MPTP induced culture dopaminergic neurons toxicity.Studies showed that pretreatment with CA could effectively reverse MPTP induced the atrophy of dopaminergic neuron and neuronal viability decrease.Moreover,CA pretreatment effectively reversed MPTP induced LDH,MDA,caspase 3 mRNA and protein increase and SOD decrease.The result demonstrated that the administration of CA protected against MPTP induced dopaminergic neurons toxicity and the mechanisms may be related to the protection of oxidative damage and prevention of abnormal caspase-3 increase.

关 键 词：鼠尾草酸 多巴胺神经元 MPTP CASPASE-3 氧化损伤 

分 类 号：R285.5[医药卫生—中药学]