首页|晚期糖基化蛋白产物受体在帕金森病发病中的作用

晚期糖基化蛋白产物受体在帕金森病发病中的作用

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目的 研究晚期糖基化蛋白产物受体(RAGE)在帕金森病(PD)模型小鼠发病中的作用.方法 将30只雄性C57BL/6小鼠随机分成正常对照组、1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)组与MPTP+ RAGE-siRNA组,每组10只.MPTP、正常对照组分别腹腔注射MPTP、生理盐水,连续5周;MPTP+ RAGE siRNA组提前1周向黑质定位注射RAGE-siRNA慢病毒,后续处理同MPTP组.应用免疫印迹方法检测小鼠黑质中RAGE、酪氨酸单氧化酶(TH)及环氧合酶-2(COX-2)蛋白的表达.结果 与正常对照组比较,MPTP组小鼠黑质中RAGE、COX-2蛋白的相对表达量明显增高(F=62.25、17.83,q=14.92、8.15,P<0.01),TH蛋白的相对表达量明显下降(F=8.87,q=5.85,P<0.01);与MPTP组比较,MPTP+ RAGE-siRNA组RAGE、COX-2蛋白的相对表达量明显降低(q=10.75、5.47,P<0.01),而TH蛋白表达明显升高(q=4.58,P<0.05).结论 RAGE可能通过炎症机制参与PD发病,针对RAGE的靶向治疗有望成为未来PD的治疗策略.
ROLE OF RAGE IN PATHOGENESIS OF PARKINSON'S DISEASE
Objective To investigate the role of receptor for advanced glycation end products (RAGE) in the pathogenesis of Parkinson's disease (PD).Methods A total of 30 male C57BL/6 mice were equally and randomly divided into three groups:normal control group,1-methyl-4-phenyl-1,2,3,6-tet rahydropyridine (MPTP) group,and MPTP+ RAGE-siRNA group.The MPTP group and the normal control group were injected intraperitoneally with MPTP and normal saline,respectively,for five consecutive weeks.The MPTP+RAGE-siRNA group was given RAGE-siRNA lentivirus in the substantia nigra by stereotaxic sur gery at one week before the treatment with MPTP which was the same as that for MPTP group.The expression of RAGE,tyrosine 3-monooxygenase (TH),and cyclooxygenase-2 (COX-2) in the substantia nigra of mice was measured by Western blot.Results Compared with the control group,the MPTP group had significantly higher levels of RAGE and COX-2 and a significantly lower levelofTH (F=62.25,q 14.92,P <0.01;F=17.83,q=8.15,P<0.01;F=8.87,q=5.85,P<0.01).Compared with the MPTP group,the MPTP+RAGE-siRNA group had significantly lower levels of RAGE and COX-2 and a significantly higher level ofTH (q=10.75,P<0.01;q=5.47,P<0.01;q=4.58,P<0.05).Conclusion RAGE may be involved in the pathogenesisof PD through inflammatory mechanism.RAGE as a target for therapeutic intervention of PD ispromising in the future.

Parkinson diseaseglycosylation end products, advancedtyrosine 3 monooxygenaselentivirus

王小力、孙筱璇、谢安木

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青岛大学附属医院神经内科,山东青岛 266003

帕金森病 糖基化终产物,高级 酪氨酸单氧化酶 慢病毒属

国家自然科学基金资助项目

81571225

2017

齐鲁医学杂志
青岛大学医学院

齐鲁医学杂志

影响因子:0.609
ISSN:1008-0341
年,卷(期):2017.32(2)
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