表没食子儿茶素没食子酸酯通过自噬-溶酶体途径对MPTP诱导帕金森病模型小鼠的作用  

Effect of EGCG on MPTP-induced Parkinson′s model mice via autophagy-lysosomal pathway

作　　者：周旭[1] 逯冉冉 任芳丽 彭小雨 杨新玲[1,2] ZHOU Xu;LU Ranran;REN Fangli;PENG Xiaoyu;YANG Xinling(Department of Neurology,the Second Affiliated Hospital of Xinjiang Medical University,Urumqi 830028,Xinjiang,China;不详)

机构地区：[1]新疆医科大学第二附属医院神经内科,新疆乌鲁木齐830028 [2]新疆医科大学,新疆乌鲁木齐830054

出　　处：《实用医学杂志》2025年第8期1097-1104,共8页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:82371258);新疆维吾尔自治区研究生研究创新基金资助项目(编号:XJ2024G161)。

摘　　要：目的探究表没食子儿茶素没食子酸酯(epigallocatechin gallate,EGCG)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)所诱导帕金森病模型小鼠的保护作用。方法将28只6~8周龄的雄性C57BL/6J小鼠随机分为4组:对照组、模型组及EGCG低剂量组[25 mg/(kg·d)]和EGCG高剂量组[50 mg/(kg·d)]。连续7 d腹腔注射MPTP 30 mg/(kg·d)制备PD小鼠模型。通过行为学指标检测、Western blot方法分析EGCG对MPTP诱导的PD模型小鼠的保护作用。结果(1)在行为学检测中,与模型组比较,经EGCG低、高治疗后小鼠的运动路程和速度得到明显改善(均P<0.001),经EGCG高剂量治疗组的小鼠在中心路程所占百分比中也呈现出显著优势(P<0.001)。(2)与对照组相比,模型组α-突触核蛋白沉积明显增加(P<0.001);与模型组相比,EGCG低、高剂量组均降低了α-突触核蛋白沉积(均P<0.001)。(3)与对照组相比,模型组小鼠黑质区Beclin 1和LC3蛋白表达量显著减少(均P<0.001),p62蛋白表达量显著增加(P<0.001);经EGCG治疗后,与模型组相比,EGCG低剂量组小鼠Beclin 1和LC3蛋白表达量有不同程度的增加(P<0.01;P<0.001),p62蛋白表达量显著下降(P<0.001),EGCG高剂量组小鼠Beclin 1和LC3蛋白表达量有显著的增加(均P<0.001),p62蛋白表达量显著下降(P<0.001)。结论EGCG通过自噬-溶酶体途径降低了α-突触核蛋白的沉积,对MPTP诱导的PD模型小鼠起到了保护作用。Objective To investigate the protective effect of epigallocatechin gallate(EGCG)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease model mice.Methods Twenty-eight male C57BL/6J mice aged 6~8 weeks were randomly divided into four groups:the control group,the model group,the low-dose EGCG group[25 mg/(kg·d)],and the high-dose EGCG group[50 mg/(kg·d)].A Parkin-son's disease(PD)mouse model was established by intraperitoneal injection of MPTP at a dose of 30 mg/(kg·d)for 7 consecutive days.The protective effect of EGCG on MPTP-induced Parkinson's model mice was analyzed through behavioral index detection and Western blot method.Results(1)In the behavioral tests,compared with the model group,the movement distance and speed of mice treated with low-and high-dose EGCG were significantly improved(both P values<0.001).The mice in the high-dose EGCG treatment group also showed a significant advantage in the percentage of the central path distance(P<0.001).(2)Compared with the control group,the deposition ofα-synuclein in the model group increased significantly(P<0.001).Compared with the model group,both the low-and high-dose EGCG groups reduced the deposition ofα-synuclein(both P<0.001).(3)Compared with the control group,the expression levels of Beclin 1 and LC3 proteins in the substantia nigra region of mice in the model group decreased significantly(both P<0.001),while the expression level of p62 protein increased significantly(P<0.001).After treatment with EGCG,compared with the model group,the expression levels of Beclin 1 and LC3 proteins in mice of the low-dose EGCG group increased to varying degrees(P<0.01;P<0.001),and the expression level of p62 protein decreased significantly(P<0.001).In the high-dose EGCG group,the expression levels of Beclin 1 and LC3 proteins increased significantly(both P<0.001),and the expression level of p62 protein decreased significantly(P<0.001).Conclusion EGCG reduces alpha-synuclein deposition via the autophagy-lysosomal pathway and protects against MP

关 键 词：帕金森病 Α-突触核蛋白 表没食子儿茶素没食子酸酯 自噬 自噬-溶酶体途径 1-甲基-4-苯基-1 2 3 6-四氢吡啶 

分 类 号：R742.5[医药卫生—神经病学与精神病学]