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 models with lipopolysaccharide-induced Parkinson's disease

作　　者：叶钦勇[1] 徐评议[2] 刘焯霖[2] 徐浩文[2] 朱蔚文[2] 杨海华[2] 

机构地区：[1]福建医科大学附属协和医院神经内科,福州350001 [2]中山大学附属第一医院神经内科,广州510080

出　　处：《中华神经医学杂志》2007年第12期1208-1213,共6页Chinese Journal of Neuromedicine

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(DA)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(n=10),并设5只生理盐水注射作为对照组,于不同时间点观察各组大鼠行为学改变,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组在LPS诱导后7d、14d的旋转次数均较单纯LPS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"分枝样"Mic;LPS诱导后两组术侧中脑OX-42蛋白水平较对照组均明显增高,LPS+Mino组增加水平显著低于单纯LPS组(P<0.01);2组术侧中脑TH阳性神经元数量、mRNA、蛋白水平均较对照组明显下降,单纯LPS组下降水平显著高于LPS+Mino组(P<0.01)。结论Mino干预可显著抑制LPS诱导的Mic激活,减轻LPS对黑质DA能神经元的毒性作用。Objective To investigate the inhibitory effect of minocycline （Mino） on lipopolysaccharide （LPS）-induced activation of microglias and its srbsequent protective effects on nigral dopaminergic neurons. Methods A total of 25 male Sprague-Dawley （SD） rats were randomly allocated into three groups, sole LPS intervention group （LPS group）（n=10）, LPS＋Mino intervention group （n=10）（LPS＋Mino group） and 5 rats injected with normal saline as the control group. Behavioral changes of all the rats were observed at 7 and 14 d, and the immunohistochemistry, in situ hybridization and Western blot were applied to observe the activation of microglias and the expression levels of positive neurons, mRNA and protein of tyrosine hydroxylase （TH） and OX-42. Results The rotation time of the LPS＋Mino group was significantly lower than that of the LPS group at 7 and 14 d; the majority of microglias were activated in both the LPS and LPS＋Mino groups, and the number of ＂amoeboid＂ microglias in the latter group was obviously lower than that in the former group, a few ＂ramified＂ microglias still existing in the latter group; Western blot assay showed that the protein levels of OX-42 expressed in the operative side midbrain of the two groups after induction were significantly higher than that in the control group, and the increment of （0.91 ±0.04） in the LPS＋Mino group was significantly lower than that of （1.03±0.03） in the LPS group （P〈0.01）; the number of TH positive neurons and the levels of TH mRNA and protein in the operative side midbrain of both groups after LPS treatment were obviously lower than in the control group, and the decreases of （21.54±4.89,39.87±7.03 and 0.42±0.03） in the LPS group were significantly higher than that of （53.41±8.36,65.12±9.06 and 0.63±0.04） in the LPS＋Mino group （P〈0.01）. Conclusion Mino may protect nigral dopaminergic neurons against lipopolysaccharide-induced neurotoxicity by inhibiting microglia activation and subsequen

关 键 词：美满霉素 脂多糖 多巴胺能神经元 小胶质细胞 帕金森病 

分 类 号：R742.5[医药卫生—神经病学与精神病学]