深部脑刺激丘脑底核治疗帕金森病大鼠脑中钙调蛋白的变化  

Calbindin-28 in rats of Parkinson's disease after deep brain stimulation to subthaiamus nucleus

作　　者：曹春燕[1] 刘振国[2] 陈生弟[3] 孙伯民[4] 占世坤[4] 陆国强[3] 

机构地区：[1]同济大学医学院生理教研室,上海200092 [2]上海交通大学医学院附属新华医院神经内科 [3]上海交通大学医学院附属瑞金医院神经内科 [4]上海交通大学医学院附属新华医院神经外科

出　　处：《中华神经科杂志》2007年第10期692-696,共5页Chinese Journal of Neurology

基　　金：上海市科学技术委员会重点资助项目(044119623)

摘　　要：目的研究慢性高频电刺激帕金森病(Parkinson's disease,PD)大鼠丘脑底核治疗 PD的机制。方法通过6-羟基多巴立体定向注射至大鼠中脑前脑束建立偏侧 PD 动物模型,对造模成功的 PD 大鼠模型丘脑底核进行高频电刺激,观察高频电刺激对 PD 大鼠行为的影响,并用蛋白印迹法检测纹状体酪氨酸羟化酶(TH)、钙调蛋白 Calbindin-28和突触前膜囊泡蛋白(synaptophysin)的表达情况。此外,对接受慢性高频电刺激的6-羟基多巴损伤纹状体双侧 PD 大鼠的脑片进行免疫组化染色,检测黑质 Calbindin-28和突触前膜囊泡蛋白的表达情况。结果 (1)高频电刺激偏侧 PD 大鼠丘脑底核可使阿朴吗啡诱导的旋转行为减少31%;(2)偏侧 PD 大鼠损伤侧纹状体内已无 TH 表达,慢性高频电刺激同侧斤.脑底核对纹状体 TH 缺失无逆转,但增加健纹状体内 TH 表达量78.6%±9.5%;(3)偏侧 PD 大鼠损伤侧纹状体内 Calbindin-28表达量增加75.4%±15.0%,慢性高频电刺激使其表达量减少43.0%±7.1%;(4)慢性高频电刺激亦显著抑制双侧 PD 大鼠黑质 Calbindin-28表达:假手术大鼠、PD 大鼠以及慢性高频电刺激后 PD 大鼠黑质致密部 Calbindin-28阳性神经元分别为74.5±10.2、75.7±15.6和33.1±7.8;(5)慢性高频电刺激未影响黑质和纹状体内突触前膜囊泡蛋白的表达。结论深部脑刺激治疗 PD 的机制与调节黑质和纹状体内钙调蛋白 Calbindin-28和 TH 表达量有关。Objective To explore the mechanism of deep brain stimulation （DBS） therapy to Parkinson＇s disease （PD）. Methods We produced hemi-parkinsonian rat model with stereotaxically injecting 6-OHDA to right medial forebrain bundle （MFB） and stimulated ipsilateral subthalamu nucleus （STN） with platinum electrodes chronically to investigate the influence of DBS to the expression of Calbindin-28, synaptophysin and tyrosine dioxydase （TH） in Striatum by Western blot. In addition, slices of bilateral PD rats after DBS were stained to observe the expression of Calbindin-28 and synaptophysin in substantia nigra by Immunohistochemistry. Results High frequency stimulation impaired the rotational frequency 31% of unilateral PD rats triggered by apomophine; Long-term DBS increased the expression of TH in innocent striatum of unilateral PD rats 78.6% ± 9. 5% , since the ipsilateral striatum （lesion side） was TH depleted by 6-OHDA insults; Calbindin-28 expression in ipsilateral striatum of hemi-PD rats raised up 75.4% ± 15.0% and long-term DBS reduced the effect by 43.0% ± 7.1%, meanwhile Calbindin-28 positive neurons in substantia nigra compacta in sham, PD and DBS rats were 74. 5 ± 10. 2, 75.7 ± 15.6, 33.1 ± 7.8. However, Synaptophysin expression in substantia nigra and striatum kept stable even after longterm DBS. Conclusions Consistent to the treatment to PD patients, DBS to STN alleviated the motor disorder of PD rats, the treatment might be based on regulating the expression of Calbindin-28 and TH.

关 键 词：帕金森病 电刺激疗法 丘脑底核 钙结合蛋白 突触囊泡蛋白 

分 类 号：R742.5[医药卫生—神经病学与精神病学]