人参皂苷Rg1对LRRK2突变致帕金森病果蝇的治疗作用探讨

Therapeutic Effect of Ginsenoside Rg1 on LRRK2 Mutations in the Drosophila Model of Parkinson’s Disease

探讨人参皂苷Rg1对LRRK2突变致帕金森病果蝇模型的脑神经保护作用及其机制。使用TH-GAL4;UAS-LRRK2-1915T品系果蝇(简称1915T)进行实验,使用1915T品系果蝇作为病理模型组,TH-GAL4品系果蝇作为阴性对照组。给予不同浓度的人参皂苷Rg1,饲养一定时间后,将帕金森综合征(parkinson'ssyndrome,PD)病理模型组与对照组进行比较,利用果蝇寿命实验,检测生命周期,筛选最佳药物作用浓度。利用该浓度进一步检测神经元凋亡,同时取果蝇头部提取蛋白质,采用Westernblot方法检测P-LRRK2、Nrf2、GCLC、P-P38MAPK、ERK、TH等蛋白表达的变化。结果表明:人参皂苷Rg1最佳药物浓度确定为0.4mmol/L,将0.4mmol/L人参皂苷Rg1于果蝇幼虫发育时期和成虫发育时期同时给与药物干预后,可以显著挽救LRRK2突变导致的果蝇存活率降低、爬行能力降低以及多巴胺含量的降低。人参皂苷Rg1能有效降低PD模型果蝇的病理症状,作用途径可能是通过其作用于P-38信号通路以保护PD中的多巴胺能神经元。

The neuroprotective effect and mechanism of ginsenoside Rg1 on LRRK2 mutation-induced drosophila model of drosophila melanogaster was studied.TH-GAL4;UAS-LRRK2-1915T strain drosophila (abbreviated as 1915T) was used for the experiment. The 1915T strain drosophila was used as the pathological model group, and the TH-GAL4 strain drosophila was used as the negative control group. Different concentrations of ginsenoside Rg1 were administered. After a certain period of time, the pathological model group of parkinson's syndrome (PD) was compared with the control group, and the life cycle was tested by drosophila life test to select the optimal drug concentration.Neuronal apoptosis was further detected by screening the optimal concentration of the drug. At the same time, the protein was extracted from the head of drosophila, and the expression of P-LRRK2, Nrf2, GCLC, P-P38MAPK, ERK, TH and other proteins were detected by Western blot.The optimal drug concentration of ginsenoside Rg1 was determined to be 0.4 mmol/L.Simultaneous treatment of drosophila during larval development and adult development with 0.4 mmol/L ginsenoside Rg1 significantly reduced the survival rate of drosophila, decreased crawling ability and decreased dopamine content caused by LRRK2 mutation.Ginsenoside Rg1 may protect dopaminergic neurons in PD by P-38 signaling pathway to reduce pathological symptoms of PD model drosophila.