白藜芦醇对6ohda诱导帕金森病大鼠模型的保护作用及其机制研究-protective effect of resveratrol on 6 - ohda - induced parkinsons disease rat model and its mechanism.docxVIP

遵义医学院2006届研究生毕业论文 白藜芦醇对6--OHDA诱导的帕金森病大鼠模型保护作用及机制研究白藜芦醇对6--OHDA诱导帕金森病大鼠模型 的保护作用及其机制研究摘要目的研究白藜芦醇(resveratrol，Res)对帕金森病(parkinson’S disease，PD)大鼠模 型的保护作用，并探讨其作用机制。方法采用6-OHDA纹状体两点注射法制作PD 大鼠模型。利用PD大鼠旋转跟踪记录系统检测大鼠旋转行为；利用光化学法检 测大脑组织中SOD、GSH—PX活性以及MDA含量；RT-PCR法检测黑质纹状体 COX．2、TNF—a、iNOS、HO—l、GNDF、BDNF及CHKmRNA的表达情况；Westernblotting检测黑质纹状体COX．2蛋白的表达。电镜下观察黑质纹状体神经元超微 结构的改变：结果Res治疗10周后，与PD模型组比较，Res治疗组大鼠旋转圈数均明显减少00．01)，效果优于ⅥtE组：与模型对照组比较，Res及VitE可增加大 鼠脑组织内SOD、GSH．PX活性，降低MDA含量： RT-PCR结果显示PD模型 对照组黑质纹状体内COX．2、TNF—a、iNOS、HO—l、GDNF、BDNF及CHKmRNA 的表达明显增多，Res抑制上述因子mRNA的表达。Western blotting结果显示PD模型组COX．2蛋白表达明显高于正常对照组，而Res治疗组能抑制该蛋白的表达。 电镜下见PD大鼠损伤侧黑质纹状体大量神经元出现变性、坏死及脱失，线粒体肿 胀呈空泡样变，内质网扩张，核边界模糊，染色质浓缩成块状聚集在核周围，而 Res和vitE治疗组可见神经元数量多于模型组，线粒体仅轻度肿胀及空泡样变，内 质网轻度扩张，核边界模糊，染色质较均匀：结论Res对6-OHDA诱导的PD大 鼠模型具有保护作用，其机制可能与Res的抗氧化作用、减轻炎症反应及促进细胞 分化有关。关键词： 自藜芦醇：6-OHDA；抗氧化：炎症反应：细胞分化：帕金森病：大鼠遵义医学院2006届研究生毕业论文 白藜芦醇对6--OHDA诱导的帕金森病大鼠模型保护作用及机制研究Protective effects of Res on rat model with PD induced by 6．OHDA and explore it’S mechanismsAbstractobjective To observe protective effects of Res on rat model、Ⅳitll PD．and explore it’S mechanisms．Methods the model was induced by injecting 6-OHDA into the dexter striatum of SD rats．RomtionM tracking system of PD rat Was used to examine the rotational frequency(RF)of the PD rats．The activity of SOD，GSH—PX and level of MDA in brain tissues were detected respectively．The levels ofCOX一2、TNF-a、iNOS、 HO—I、GDNF、BDNF and CHK mRNA were determined by RT-PCR，and the expression of COX一2 Was examined by Western blotting．The ultrastructure of substantia nigra(SN)and striatum tissues were observed by electronic microscope．Results The results showed that the RF of ratS was obvious Variante between therapeutic groups and model control at tenth week f P0．01)，which Was better thanthose in vitE伊O．05)．The average activity of SOD and GSH-PX was apparentlyhigher，the average level of MDA Was apparently lower in Res and VitE groups than those in model group．Res decreased the levels of COX·2、田NF—a、iNOS、HO-1、