骨化三醇对脂多糖诱导帕金森病大鼠黑质多巴胺能神经元的保护作用  

Neuroprotectvie Effect of Calcitriol on Rat Parkinson's Disease Model Induced with Lipopolysaccharide

作　　者：杜望春[1] 陆惠平 杨涛 

机构地区：[1]上海健康医学院临床医学院,201318 [2]上海市浦东医院药剂科,200120

出　　处：《中国临床神经科学》2015年第5期526-530,共5页Chinese Journal of Clinical Neurosciences

基　　金：上海交通大学医学院科技基金(编号:11XJ21040)

摘　　要：目的探讨骨化三醇对多巴胺能神经元的保护作用及其可能机制。方法用骨化三醇腹腔注射治疗脂多糖(LPS)偏侧帕金森病(PD)模型大鼠。成年雄性SD大鼠60只随机分为4组1对照组:右侧黑质致密部立体定向注射2μL生理盐水;2 LPS模型组:右侧黑质致密部立体定向注射LPS 2μL(5μg·μL-1);3骨化三醇高剂量组:LPS造模前7 d和造模后14 d,分别腹腔注射骨化三醇0.1μg·kg-1;4骨化三醇低剂量组:LPS造模前7 d和造模后14 d,分别腹腔注射骨化三醇0.05μg·kg-1。每组大鼠均n=15。观察阿扑吗啡诱导的PD大鼠旋转行为变化,免疫荧光组化学法检测黑质酪氨酸羟化酶(TH)的表达,ELISA法测定黑质区炎性因子(IL-1β和TNF-α)的变化。结果骨化三醇干预组大鼠旋转圈数相对于LPS模型组明显降低,其黑质TH阳性神经元存活比率显著高于LPS模型组,且能明显减少黑质中IL-1β和TNF-α的释放量。结论骨化三醇能够减轻LPS引起的大鼠多巴胺能神经元的损害,其机制与减少免疫炎症因子的释放有关。Aim To explore the neuroprotective effects and possible mechanisms of calcitriol in Parkinson＇s disease rat model induced with lipopolysaccharide（LPS）. Methods The rat were randomly divided into four groups, including a control group, a LPS group, a high-dose calcitriol group（0.1μg·kg-1） and a low-dose（0.05 μg·kg-1） calcitriol group. Apomorphine（APO） induced rotational behavior of rats were observed, and the expression of tyroxine hydroxylase neurons in the substantia nigra, as well as the level of IL-1β and TNF-αwere observed by using immunohistochemistry and ELISA box. Results After the two week treatment, highdose calcitriol significantly improved the behavioral manifestation compared with the LPS group（P 0.001）. The survival ratio of dopaminergic neurons in the high-dose calcitriol group was significantly higher than that in the LPS group（P〈0.001）. High-dose calcitriol also can significantly reduce the excessive production of IL-1βand TNF-α. Conclusion Calcitriol has a protective effect on dopaminergic neurons in substantia nigra of LPS induced PD model rats. The mechanism may be related to attenuating the neuro inflammatory process by reducing the generation of inflammatory cytokines.

关 键 词：骨化三醇 脂多糖 帕金森病 大鼠 

分 类 号：R742.5[医药卫生—神经病学与精神病学]