基础医学与临床
基礎醫學與臨床
기출의학여림상
Basic & Clinical Medicine
2015年
10期
1351-1357
,共7页
眭晨燕%李学忠%周小平%陈晓鹏
眭晨燕%李學忠%週小平%陳曉鵬
휴신연%리학충%주소평%진효붕
雌激素%帕金森病%年龄%自噬
雌激素%帕金森病%年齡%自噬
자격소%파금삼병%년령%자서
estrogen%Parkinson’s disease%age%autophagy
目的:探讨雌激素(E2)对鱼藤酮诱导的不同年龄组帕金森病(PD)大鼠模型的影响及其机制。方法将24月龄SD大鼠(高龄组)和12周龄SD大鼠(低龄组)分别分为对照组(0.9%氯化钠溶液)、鱼藤酮处理组(鱼藤酮2 mg/kg)、雌激素治疗组(鱼藤酮2 mg/kg和E21 mg/kg)和他莫昔芬处理组(鱼藤酮2 mg/kg、E21 mg/kg和他莫昔芬1 mg/kg),用行为学测试观察大鼠运动功能改变,免疫组织化学法及Western blot检测TH及LC-3表达,高效液相色谱-电化学检测仪(HPLC-ECD)检测纹状体单胺类递质的变化。结果1)鱼藤酮显著缩短高龄大鼠转棒潜伏期,延长爬杆时间(P<0.05),雌激素减弱鱼藤酮作用,他莫昔芬减轻雌激素作用。2)鱼藤酮显著减少高龄组黑质TH阳性细胞数和TH表达( P<0.05),雌激素逐渐恢复TH 阳性细胞损失和TH表达,他莫昔芬减轻雌激素作用。3)鱼藤酮增加LC-3表达(P<0.05),雌激素和他莫昔芬对其表达影响不大。4)鱼藤酮显著降低DA及其代谢产物DOPAC含量(P<0.05),升高5-HT含量,高龄组更明显(P<0.05),雌激素减弱鱼藤酮作用,他莫昔芬减轻雌激素作用。5)鱼藤酮增加自噬体的数量,雌激素增加自噬溶酶体/自噬体的比例。结论高龄大鼠PD模型更可靠,雌激素通过促进自噬成熟对鱼藤酮诱导的大鼠PD模型产生明显的治疗作用。
目的:探討雌激素(E2)對魚籐酮誘導的不同年齡組帕金森病(PD)大鼠模型的影響及其機製。方法將24月齡SD大鼠(高齡組)和12週齡SD大鼠(低齡組)分彆分為對照組(0.9%氯化鈉溶液)、魚籐酮處理組(魚籐酮2 mg/kg)、雌激素治療組(魚籐酮2 mg/kg和E21 mg/kg)和他莫昔芬處理組(魚籐酮2 mg/kg、E21 mg/kg和他莫昔芬1 mg/kg),用行為學測試觀察大鼠運動功能改變,免疫組織化學法及Western blot檢測TH及LC-3錶達,高效液相色譜-電化學檢測儀(HPLC-ECD)檢測紋狀體單胺類遞質的變化。結果1)魚籐酮顯著縮短高齡大鼠轉棒潛伏期,延長爬桿時間(P<0.05),雌激素減弱魚籐酮作用,他莫昔芬減輕雌激素作用。2)魚籐酮顯著減少高齡組黑質TH暘性細胞數和TH錶達( P<0.05),雌激素逐漸恢複TH 暘性細胞損失和TH錶達,他莫昔芬減輕雌激素作用。3)魚籐酮增加LC-3錶達(P<0.05),雌激素和他莫昔芬對其錶達影響不大。4)魚籐酮顯著降低DA及其代謝產物DOPAC含量(P<0.05),升高5-HT含量,高齡組更明顯(P<0.05),雌激素減弱魚籐酮作用,他莫昔芬減輕雌激素作用。5)魚籐酮增加自噬體的數量,雌激素增加自噬溶酶體/自噬體的比例。結論高齡大鼠PD模型更可靠,雌激素通過促進自噬成熟對魚籐酮誘導的大鼠PD模型產生明顯的治療作用。
목적:탐토자격소(E2)대어등동유도적불동년령조파금삼병(PD)대서모형적영향급기궤제。방법장24월령SD대서(고령조)화12주령SD대서(저령조)분별분위대조조(0.9%록화납용액)、어등동처리조(어등동2 mg/kg)、자격소치료조(어등동2 mg/kg화E21 mg/kg)화타막석분처리조(어등동2 mg/kg、E21 mg/kg화타막석분1 mg/kg),용행위학측시관찰대서운동공능개변,면역조직화학법급Western blot검측TH급LC-3표체,고효액상색보-전화학검측의(HPLC-ECD)검측문상체단알류체질적변화。결과1)어등동현저축단고령대서전봉잠복기,연장파간시간(P<0.05),자격소감약어등동작용,타막석분감경자격소작용。2)어등동현저감소고령조흑질TH양성세포수화TH표체( P<0.05),자격소축점회복TH 양성세포손실화TH표체,타막석분감경자격소작용。3)어등동증가LC-3표체(P<0.05),자격소화타막석분대기표체영향불대。4)어등동현저강저DA급기대사산물DOPAC함량(P<0.05),승고5-HT함량,고령조경명현(P<0.05),자격소감약어등동작용,타막석분감경자격소작용。5)어등동증가자서체적수량,자격소증가자서용매체/자서체적비례。결론고령대서PD모형경가고,자격소통과촉진자서성숙대어등동유도적대서PD모형산생명현적치료작용。
Objective_To investigate the effect of estrogen(E2) on different age rat groups of Parkinson’s disease (PD) models induced by Rotenone and its mechanism.Methods_24-month-old SD rats(high age group)and 12-week-age SD rats( low age group ) were divided into control group ( saline ) , Rotenone treatment group ( Rotenone 2 mg/kg), Estrogen treatment group(Rotenone 2 mg/kg and E2 1 mg/kg)and Tamoxifen treatment group(Rote-none 2 mg/kg, E2 1 mg/kg and Tamoxifen 1 mg/kg).Behavior tests were carried out to observe the change of movement function, Immunohistochemistry and Western blot were used to assess the changes of TH and LC-3. HPLC-ECD was used to detect possible changes of monoamine neurotransmitters in striatum.Results_1) Rotenone reduced significantly old age rat’s rotarod latencies and prolonged the climbing pole time(P<0.05).E2 ameliorated this effect, Tamoxifen reduced the effect of E2.2) Rotenone significantly reduced the number of TH positive cells in <br> high age rats(P<0.05), E2 partly restored TH positive cell loss, Tamoxifen reduced this effect of E2, so did the ex-pression of TH protein.3)Rotenone increased the expression of LC-3(P<0.05), E2 did not affect the expression of LC-3, so did Tamoxifen.4)Rotenone significantly decreased the level of DA and its metabolite DOPAC(P<0.05), elevated the level of 5-HT especially in old rats(P<0.05).E2 downregulated the influence, and Tamoxifen reduced the effect of E2.5)Rotenone increased the number of autophagosomes, but E2 increased the proportion of autolyso-somes/autophagosomes.Conclusions_Old age rat PD model was more reliable.Estrogen promoted autophagy ma-ture, and had obvious therapeutic effect on rat PD model induced by rotenone.