雌激素对不同年龄组帕金森病大鼠的影响及其机制

摘要

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。%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 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.