中药药理与临床2025，Vol.41Issue(6)：19-24,6.
芍地帕宁方对帕金森病A53T小鼠中脑黑质多巴胺神经元铁死亡的影响
Effect of Shaodi Paning(芍地帕宁)Decoction on Ferroptosis of Dopamine Neurons of Substantia Nigra in A53T Mouse Model of Parkinson's Disease
摘要
Abstract
Objective:To investigate the effect of Shaodi Paning(芍地帕宁)Decoction(SDPND)on dopaminergic neurons in the mouse model of Parkinson's disease(PD)and its underlying mechanism.Methods:Forty 10-month-old A53T mice were randomized into model,SDPND(34.2,17.1,and 8.6 g/kg),and levodopa and benserazide(0.1 g/kg)groups(n=8),and eight C57/BL6 mice of 10 months old were se-lected as the blank group.After modeling,mice in each group were orally administrated with corresponding drugs or saline water,once per day for 28 days.After administration,the hang test and lower limb gripping test were carried out to evaluate the behavioral changes of mice.The expression of the dopaminergic neuron marker tyrosine hydroxylase(TH)in the midbrain substantia nigra was detected by immunohistochem-istry.The morphological changes of mitochondria were observed by transmission electron microscopy.The levels of glutathione(GSH),reactive oxygen species(ROS),superoxide dismutase(SOD),and malondialdehyde(MDA)in the serum were determined by colorimetry.Western blotting and PCR were employed to determine the protein and mRNA levels of ferroptosis markers in substancia nigra.Results:Compared with the blank group,the model group showed shortened rod gripping duration,increased lower limb gripping function score,decreased TH-positive cells,increased mitochondrial vacuoles,lowered levels of GSH and SOD,elevated levels of MDA and ROS,up-regulated protein and mRNA levels of ferroportin 1(FPN1)and divalent metal-ion transporter-1(DMT1),and down-regulated protein and mRNA levels of nuclear factor-erythroid 2-related factor 2(Nrf2),solute carrier family 7 member 11(SLC7A11),and glutathione peroxidase 4(GPX4)(P<0.05).Com-pared with the model group,the SDPND and levodopa and benserazide(0.1 g/kg)groups showed prolonger gripping duration,decreased low-er limb gripping function score,increased TH-positive cells,reduced mitochondrial vacuoles,elevated levels of GSH and SOD,lowered levels of MDA and ROS,down-regulated protein and mRNA levels of FPN1 and DMT1,and up-regulated protein and mRNA levels of Nrf2,SLC7A11,and GPX4(P<0.05).Conclusion:SDPND can alleviate oxidative damage in the treatment of PD by inhibiting ferroptosis.关键词
芍地帕宁方/帕金森病/中脑黑质/铁死亡/膜铁转运蛋白l/二价金属离子转运体1/胱氨酸/谷氨酸逆向转运蛋白溶质载体家族7成员11Key words
Shaodi Paning(芍地帕宁)Decoction/Parkinson's disease/Midbrain substantia nigra/Ferroptosis/FPN1/DMT1/SLC7A11引用本文复制引用
董薇,杨文明,郝文杰,胡胜,王倩,朱倩倩..芍地帕宁方对帕金森病A53T小鼠中脑黑质多巴胺神经元铁死亡的影响[J].中药药理与临床,2025,41(6):19-24,6.基金项目
国家中医药传承创新中心项目(发改办社会[2022]366号) （发改办社会[2022]366号）
安徽高校协同创新项目(编号:GXXT-2020-025). （编号:GXXT-2020-025）
