美满霉素对脂多糖诱导帕金森病模型多巴胺能神经元保护作用的研究  

Minocycline protects dopaminergic neurons in lipopolysaccharide.induced model of Parkinson' s disease

作　　者：叶钦勇[1] 杨海华[1] 徐评议[1] 刘焯霖[1] 徐浩文[1] 朱蔚文[1] 谢安木[1] 

机构地区：[1]中山大学第一医院神经内科

出　　处：《中华神经科杂志》2007年第2期124-128,共5页Chinese Journal of Neurology

基　　金：国家自然科学基金(30370509;30570645)

摘　　要：目的探讨美满霉素(Mino)对脂多糖(LPS)诱导小胶质细胞(Mic)激活的抑制作用和对黑质多巴胺能神经元的保护作用。方法 20只雄性 SD 大鼠随机分为单纯 LPS 干预组和 LPS+Mino 干预组,并设5只作为生理盐水注射对照组,于不同时间点观察大鼠行为学改变,并采用免疫组织化学、原位杂交、Western-blot 等方法观察 Mic 的激活情况以及酪氨酸羟化酶(TH)神经元、mRNA、蛋白的表达水平。结果 LPS+Mino 干预组在 LPS 诱导后7、14 d 的旋转次数均较单纯 LPS 干预组明显减少;两组均以激活型 Mic 为主,LPS+Mino 组"阿米巴样"Mic 数目较单纯 LPS 组明显减少,尚存有少许"分支样"Mic;LPS 术后2组术侧中脑 OX-42蛋白水平较生理盐水注射对照组均明显增高,LPS+Mino 组(0.91±0.04)增加水平明显低于单纯 LPS 组(1.03±0.03,P<0.01);2组术侧中脑 TH阳性神经元数量、mRNA、蛋白水平均较生理盐水注射对照组明显下降,单纯 LPS 组(21.5±4.9,39.9±7.0,0.42±0.03)下降水平显著高于 LPS+Mino 组(53.4±8.4,65.1±9.1,0.63±0.04;P<0.01)。结论 Mino 的干预可显著抑制 LPS 诱导的 Mic 激活,减轻 LPS 对黑质多巴胺能神经元的毒性作用,并延缓 PD 模型的病情进展。Objective To further investigated the effect of minocycline on the inhibition of microglial activation and subsequent protection of nigral DA neuron. Methods 20 rats injected with LPS in the substantia nigra （SN） were randomly divided into two groups （ LPS group and LPS ＋ Minocychne group）. The behavior was observed on the 7^th d and 14^th d. The immunohistochemistry, in situ hybridization and Western-blot were used to detect the levels of positive neuron, mRNA, protein of TH and OX-42, Results The slightly rotational behavior was observed in LPS ＋ Minocycline group, The majority of microglias were activated in the two groups . Some microglia in the SNpc remained ramified in LPS ＋ Minocycline group. The numbers of hypertophic microglia in LPS ＋ Minocycline group were less than that in LPS group. Western-blot showed that the protein of OX-42 in two LPS groups was higher than in normal group（P 〈0.01）,and the degree of increment in LPS group（1.03 ±0.03） was more than that in LPS ＋ Minocycline group（0.91 ±0.04）（P 〈0.01）. The numbers of TH positive neurons and the level of TH mRNA, protein of TH in the two LPS groups were lower than that in normal group （ P 〈 0. 01 ）, and the degree of decrease in LPS group （ 21.54 ± 4. 89,39. 87 ± 7.03,0. 42 ± 0. 03 ） was more than in LPS ＋ Minocycline group（53.41 ±8.36,65.12 ±9.06,0.63 ±0.04）（P〈0.01）. Conclusion Minocycline, inhibiting microglial activation, has a strong neuroprotective activity and prevents the progression of the LPS- induced model of PD.

关 键 词：米诺环素 脂多糖类 神经保护药 小神经胶质细胞 帕金森病 

分 类 号：R742.5[医药卫生—神经病学与精神病学]