CAJ | 학술논문

目的：观察百可利对6-羟多巴胺（6-OHDA）内侧前脑束（MFB）和纹状体尾壳核（CPu）两个不同注射位点帕金森病（PD）模型大鼠的治疗作用，两个注射位点模型分别记为：MFB-M，CPu-M。方法运用6-OHDA两点注射法，损毁大鼠左侧中脑多巴胺能神经元，制备PD模型。记录大鼠后肢肌电（EMG）信号频率观察肌肉震颤；测定大鼠自主活动；电化学法检测纹状体内多巴胺（DA）及其代谢产物含量；免疫组化法检测大鼠脑内酪氨酸羟化酶（TH）、OX-42表达；观察神经元超微结构变化。结果给药3周后，两个注射位点的模型组行为改变趋势一致，百可利在两个注射位点的模型动物上药效表现不同，在CPu-M组可明显提高PD大鼠自主活动数（P＜0.05）。EMG信号分析显示，在MFB-M组，给予百可利，肌电频率降低55％；在CPu-M组，给予百可利，肌电频率降低60％。EMG时效研究表明，在 CPu-M组，百可利药效持续420 min以上。纹状体递质水平显示，两个注射位点的模型组DA递质水平差异很大，在CPu-M组，百可利能够明显升高DA水平（P＜0.05）。两个注射位点的模型组免疫组织化学结果趋势一致，在CPu-M组，百可利有更明显神经元保护作用（P＜0.05），在MFB-M组，百可利抑制小胶质细胞过度激活作用更强（P＜0.01）。结论不同注射位点制备的PD模型能够反映不同时期PD的病理变化，百可利可通过抑制炎性介质生成和释放、保护残存神经元、恢复神经元功能等机制改善PD不同发病时期模型动物的行为学症状。
목적：관찰백가리대6-간다파알（6-OHDA）내측전뇌속（MFB）화문상체미각핵（CPu）량개불동주사위점파금삼병（PD）모형대서적치료작용，량개주사위점모형분별기위：MFB-M，CPu-M。방법운용6-OHDA량점주사법，손훼대서좌측중뇌다파알능신경원，제비PD모형。기록대서후지기전（EMG）신호빈솔관찰기육진전；측정대서자주활동；전화학법검측문상체내다파알（DA）급기대사산물함량；면역조화법검측대서뇌내락안산간화매（TH）、OX-42표체；관찰신경원초미결구변화。결과급약3주후，량개주사위점적모형조행위개변추세일치，백가리재량개주사위점적모형동물상약효표현불동，재CPu-M조가명현제고PD대서자주활동수（P＜0.05）。EMG신호분석현시，재MFB-M조，급여백가리，기전빈솔강저55％；재CPu-M조，급여백가리，기전빈솔강저60％。EMG시효연구표명，재 CPu-M조，백가리약효지속420 min이상。문상체체질수평현시，량개주사위점적모형조DA체질수평차이흔대，재CPu-M조，백가리능구명현승고DA수평（P＜0.05）。량개주사위점적모형조면역조직화학결과추세일치，재CPu-M조，백가리유경명현신경원보호작용（P＜0.05），재MFB-M조，백가리억제소효질세포과도격활작용경강（P＜0.01）。결론불동주사위점제비적PD모형능구반영불동시기PD적병리변화，백가리가통과억제염성개질생성화석방、보호잔존신경원、회복신경원공능등궤제개선PD불동발병시기모형동물적행위학증상。
Aim To explore the therapeutical effect and mechanism of baicalein on two 6-hydroxydopamine (6-OHDA ) induced Parkinson′s disease (PD ) rat models,which received unilateral lesions of the left medial forebrain bundle (MFB ) or caudate putamen (CPu ) made by stereotaxic injection of 6-OHDA (MFB-M,CPu-M).Methods PD rat models were established by microinjection of 6-OHDA into MFB or CPu.The anti-tremor effect of baicalein on PD rat models was examined.Spontaneous activity was recor-ded. Dopamine (DA ), dihydroxyphenylacetic acid (DOPAC)and homovanilic acid (HVA)in striatum were quantified by HPLC-ECD.The tyrosine hydroxy-lase (TH)and OX-42 positive cells were detected by immunohistochemical method.The morphological vari-ation of the neurons was confirmed by analysis at an ul-trastructural level.Results Baicalein significantly in-creased the spontaneous activity in CPu-M.The elec-tromyography (EMG ) recordings revealed that com-pared with 6-OHDA group,the tremor frequency in ba-icalein group was decreased by 55% in MFB-M,and by 60% in CPu-M.6-OHDA treatment decreased DA levels in the striatum,while treatment with baicalein attenuated the DA decreases in CPu-M.Moreover,ba-icalein treatment could increase TH-positive neurons and decrease OX-42-postive microglia compared with 6-OHDA group in both MFB-M and CPu-M.Conclu-sions In the present study,it is illustrated that ①microinjection of 6-OHDA into the MFB and the CPu could cause different pathological changes of PD, which is important for efficacy evaluation;②baicalein showed the ability to alleviate the behavior symptoms in PD-rats at different stages by improving motor function and attenuating muscle tremor;③therapeutic effect of baicalein was produced by inhibiting the inflammatory medium production and release,anti-apoptosis,chan-ging dopamine catabolism, and inhibiting dopamine turnover.