灵芝孢子油对MPTP处理小鼠行为学及黑质区病理变化的影响

南方医科大学学报 ›› 2005, Vol. 25 ›› Issue (06): 667-671.

灵芝孢子油对MPTP处理小鼠行为学及黑质区病理变化的影响

朱蔚文, 刘焯霖, 徐浩文, 褚文政, 叶钦勇, 谢安木, 陈玲, 黎锦如

中山大学第一附属医院神经内科, 广东, 广州, 510080

出版日期:2005-06-20 发布日期:2005-06-20
基金资助:
收稿日期:2005-1-9。
基金项目:广东省自然科学基金(21868)
作者简介:朱蔚文(1971- ),女,在读博士研究生,主治医师,主要研究方向:帕金森病、癫痫的临床和基础研究,E-mail:zhuweiwen11@126.com

Effect of the oil from ganoderma lucidum spores on pathological changes in the substantia nigra and behaviors of MPTP-treated mice

ZHU Wei-wen, LIU Zhuo-lin, XU Hao-wen, CHU Wen-zheng, YE Qin-yong, XIE An-mu, CHEN Ling, LI Jin-ru

中山大学第一附属医院神经内科, 广东, 广州, 510080

Online:2005-06-20 Published:2005-06-20

摘要/Abstract

摘要： 目的研究灵芝孢子油对MPTP帕金森病(PD)小鼠模型行为学及病理改变的影响,探讨灵芝孢子油治疗帕金森病的可能性。方法 C57BL小鼠分为正常对照组、MPTP组、灵芝孢子油+MPTP组。MPTP组皮下注射MPTP(30mg/kg×6d)及喂食生理盐水,灵芝孢子油+MPTP组在注射MPTP前2d开始鼻饲灵芝孢子油1.5g/kg·d,连续8d。2周后用高效液相色谱法检测小鼠纹状体多巴胺(DA)及其代谢物含量,免疫组织化学法检测SNpc酪氨酸羟化酶(TH)阳性细胞数量,Westernblot法对中脑TH蛋白进行半定量测定。结果 (1)爬杆实验中肢体出现刻板抖动行为的小鼠数目比例灵芝孢子油+MPTP组较MPTP组显著减少(12.5% vs 68.7%)。(2)DA及其代谢物含量在两组间有差异,灵芝孢子油+MPTP组各项指标均高于MPTP组。(3)灵芝孢子油+MPTP组小鼠在SNpc的TH阳性细胞、中脑TH蛋白含量均较MPTP组明显增多。结论灵芝孢子油能明显改善MPTP小鼠模型行为学,增加纹状体DA及其代谢物含量,减少黑质DA能神经元的损伤,提示灵芝孢子油可能具有减缓PD病变进程的神经保护作用。

Abstract: Objective To investigate the oil from the spores of ganoderma lucidum, a rare Chinese herb, on the behaviors and pathological changes in the substantia nigra pars compacta (SNpc) in mouse models of Parkinson’s disease (PD) induced by MPTP. Methods C57BL mice were divided into 3 groups, and the ganoderma spores oil + MPTP group were treated with ganoderma spores oil for 8 days, together with subcutaneous injection of MPTP (30 mg/kg) starting on the third day for 6 days; MPTP group were pretreated with normal saline before subcutaneous MPTP injection, and the normal control group received pretreatment with normal saline before subcutaneous normal saline injection. The behavioral changes of the mice in different groups were observed by pole test, dopamine and its metabolic products in the striatum determined by HPLC, tyrosine hydroxylase (TH) positive cells detected by immunofluorescence method, and expression of TH protein by Western blotting. Results The mice in the ganoderma spores oil+MPTP group presented significantly less involuntary movement of the limbs in the pole test than the mice in MPTP group. The levels of dopamine and DOPAC in the striatum of ganoderma spores oil-treated mice were increased as compared with those in MPTP group. The number of surviving TH-positive neurons in SNpc of mice in ganoderma spores oil + MPTP group was significantly greater than that in MPTP group, with also significantly increased TH protein expression. Conclusion Ganoderma spores oil has neuroprotective effect for preventing doparminergic neuron from impairment by MPTP.

中图分类号:

R742.5

朱蔚文, 刘焯霖, 徐浩文, 褚文政, 叶钦勇, 谢安木, 陈玲, 黎锦如. 灵芝孢子油对MPTP处理小鼠行为学及黑质区病理变化的影响[J]. 南方医科大学学报, 2005, 25(06): 667-671.

ZHU Wei-wen, LIU Zhuo-lin, XU Hao-wen, CHU Wen-zheng, YE Qin-yong, XIE An-mu, CHEN Ling, LI Jin-ru. Effect of the oil from ganoderma lucidum spores on pathological changes in the substantia nigra and behaviors of MPTP-treated mice[J]. Journal of Southern Medical University, 2005, 25(06): 667-671.

参考文献

[1] Dawson TM, Dawson VL. Molecular pathways of neurodegeneration in Parkinson’s disease[J]. Science, 2003, 302(5646):819-22.
[2] Kieburtz K. Designing neuroprotection trials in Parkinson’s disease[J]. Ann Neurol, 2003, 53(suppl 3):S100-9.
[3] Schober A. Classic toxin-induced animal models of Parkinson’s disease:6-OHDAand MPTP[J]. Cell Tissue Res, 2004, 318(1):215-24.
[4] Grunblatt E, Mandel S, Youdim MB. MPTP and 6-hydroxydopamine-induced neurodegeneration as models for Parkinson’s disease:neuroprotective strategies [J]. J Neurol, 2000, 247(suppl 2):95-102.
[5] Mitsumoto Y, Watanabe A, Mori A, et al. Spontaneous regeneration of nigrostriatal dopaminergic neurons in MPTP-treated C57BL/6mice[J]. Biochem Biophys Res Commun, 1998, 248(3):660-3.
[6] Mihatsch W, Russ H, Przuntek H. Intracerebroventricular dministration of 1-methyl-4-phenylpyridinium ion in mice:effects of simultaneously administered nomifensine, deprenyl, and 1-t-butyl-4,4-diphenylpiperidine[J]. J Neural Transm, 1988, 71(3):177-88.
[7] 李德鹏,徐群渊,张进禄,等.MPTP处理的小鼠和6-OHDA损毁的大鼠帕金森病模型病理变化的比较[J].中风与神经疾病杂志,1999,16(2):79-82.Li DP, Xu QY, Zhang JL, et al. Comparison of the pathology changes between two kinds of PD animal models with MPTP-treated mice and 6-OHDA-lesioned rats [J]. J Apopl Nerv Dis, 1999, 16(2):79-82.
[8] Rascol O, Payoux P, Ory F, et al. Limitations of current Parkinson’s disease therapy[J]. Ann Neurol, 2003, 53 (Suppl 3):S3-15.
[9] 徐强,徐如祥,张世忠,等.外源性超氧化物歧化酶保护6-羟基多巴所致大鼠中脑多巴胺能神经元凋亡的实验研究[J].第一军医大学学报,2003,23(11):1156-9.Xu Q, Xu RX, Zhang SZ, et al. Protective effect of exogenous superoxide dismutase against rat midbrain dopaminergic neuron apoptosis [J]. J First Mil Med Univ/Di Yi Jun Yi Da Xue Xue Bao,2003, 23(11):1156-9.
[10] 罗俊,林志彬.灵芝三萜类化合物药理作用研究进展[J].药学学报(Acta Pharm),2002,37(7):574-8.
[11] 谢安木,刘焯霖,陈玲,等.实验性帕金森病黑质的超微结构变化及灵芝孢子粉的影响研究[J].中国神经精神疾病杂志,2004,30(1):11-3.Xie AM, Liu ZL, Chen L, et al. Study on ultrastructural changes of substantia nigra and effects of ganoderma spores on the changes in experiment Parkinson’s disease rats [J]. Chin J Nerv Ment Dis,2004, 30(1):11-3.