雌激素对不同年龄组帕金森病大鼠的影响及其机制

Effects of estrogen on rats of different age groups with Parkinson's disease and its mechanisms

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E2 1 mg/kg)和他莫昔芬处理组(鱼藤酮2 mg/kg、E2 1 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.