人参皂苷Rg1对MPTP所致亚急性帕金森病模型小鼠中脑黒质p-c-Jun与COX-2表达的影响  

Influence of Ginsenoside Rg1 on p-c-Jun and COX-2 expression in substantia nigra of the MPTP mouse model of subacute Parkinson's disease

作　　者：王永生[1] 李会[2] 张宇新[1] 韦淑萍[2] 张作风[1] 田青友[1] 

机构地区：[1]华北煤炭医学院基础医学部,唐山063000 [2]华北煤炭医学院附属医院,唐山063000

出　　处：《神经解剖学杂志》2009年第4期432-436,共5页Chinese Journal of Neuroanatomy

基　　金：河北省自然科学基金(C2004000689);河北省博士基金(05547008D-4);河北省科学技术与社会发展计划项目(04276135);唐山市科学技术研究与发展计划项目(08130217C)资助项目

摘　　要：本文研究了人参皂苷Rg1(Ginsenoside Rg1,Rg1)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine,MPTP)所致亚急性Parkinson病(PD)模型小鼠中脑黒质磷酸化c-Jun(p-c-Jun)与环氧合酶-2(cyclooxygenase-2,COX-2)表达的影响,以期探讨Rg1保护PD中脑黑质多巴胺(DA)能神经元可能的分子机制。实验采用MPTP制备亚急性PD小鼠模型。通过行为学观察,免疫组织化学SP法和免疫蛋白印迹法,观察PD模型小鼠行为学变化,中脑黑质酪氨酸羟化酶(TH)、COX-2和p-c-Jun表达水平的变化,并观察给予人参皂苷Rg1对上述变化的影响。结果显示,模型小鼠出现典型PD样症状。与对照组小鼠相比,黑质区TH阳性神经元数下降约65%(P<0.001),TH表达水平显著降低约75%;黑质区COX-2阳性细胞明显增多,p-c-Jun特异性表达于黑质区细胞核内,且COX-2与p-c-Jun表达水平均明显升高。经Rg1(10mg/kg)处理后,模型小鼠PD样症状减轻,与对照组比较,在MPTP第5次注射后7d,TH阳性细胞数和TH表达水平仅下降约15%和20%;与模型组比较,黑质区COX-2阳性细胞明显减少,p-c-Jun主要表达于细胞浆,部分表达于细胞核,表达水平也明显降低。以上实验结果表明,人参皂苷Rg1对MPTP诱导的亚急性Parkinson病小鼠中脑黑质细胞的神经保护作用可能是通过阻抑p-c-Jun核内表达,从而减弱COX-2表达及其介导的黒质区炎症反应。To investigate the effect of Ginsenoside Rgl （ Rg1 ） on the expression of p-c-Jun and COX-2 in substantia nigra （SN） of the MPTP mouse model of subacute PD and further explore the possible protective mechanism of it on DA neuronal death in PD, C57BL/6N mice were administrated with MPTP to produce subacute PD model. By using inmmunohistochmnistry and Western blot , we observed the expression changes of TH, COX-2 and p-c-Jun in SN of the midbrain. The above changes, after giving Rg1, were also studied. Meanwhile, the behavioral changes of PD mice were observed after MPTP and Rgl injections. Our results suggest that compared with the mice in control group, the PD mice had the typical symptoms of PD. The number of TH-positive neurons and expression level of TH in model group were distinctly reduced by about 65% and 75% （ P 〈0. 001 ） in the substantia nigra at 7 d after the fifth injection of MPTP. The number of COX-2 positive ceils were significantly increased and p-c-Jun was specially expressed in the nuclei of neurons in SN; the expres- sion level of p-c-Jun and COX-2 was greatly increased in SN of midbrain. But in Rgl group, the PD mice administrated by Rgl had slight behavioral symptoms. The number of TH-positive neurons and the expression level of TH in SN were only decreased by 15% and 20% as compared with the control group （ P 〈 0. 001 ） at 7 d after the fifth injection of MPTP. The number of COX-2 positive cells were clearly reduced as compared with the model group, p-c-Jun was mainly expressed in the cytoplasm of neurons with a little in the nucleus; the expression level of p-c-Jun and COX-2 in SN was clearly decreased at 6 h after the third injection of MPTP. The above results showed that the neuroprotective mechanism of Rg1 might be mediated by blocking the expression of p-c-Jun in nucleus and then attenuating the inflammation reaction induced by COX-2 expression in SN in the MPTP mouse model of subacute PD.

关 键 词：PARKINSON病 人参皂苷RG1 炎症 环氧合酶-2 磷酸化c—Jun C57BL/6N小鼠 

分 类 号：R285[医药卫生—中药学]