Effects of Bushen Huoxue Granules on ferroptosis in brain nigrostriatal neurons of Parkinson's disease model mice based on NCOA4-mediated ferritinophagy
Objective:To investigate the effect of Bushen Huoxue Granules(BSHXG)on ferritinophagy-ferroptosis in MPTP-induced Parkinson's disease(PD)model mice.Methods:Seventy-two mice were randomly divided into normal group,model group,Medopar group and BSHXG high-,medium-and low-dose group,12 mice in each group,and the PD mouse model was induced by intraperitoneal injection of MPTP.The mice in each group were evaluated behaviorally using pole-climbing test and baton twirling fatigue test;transmission electron microscopy was used to detect the mitochondrial morphology of brain nigrostriatal cells;immunohistochemistry was used to detect the expression of brain nigrostriatal tyrosine hydroxylase(TH)-positive cells;immunoblotting was used to detect the expression of brain nigrostriatal NCOA4,FTH1,ACSL4,and LPCAT3 proteins;and colorimetric assay was used to detect the content of brain nigrostriatal Fe2+,T-SOD,and GSH.Results:Compared with the model group,the rod-climbing steering time and total time of mice in the Medopar and BSHXG three dose groups were shortened(P＜0.01),and the stick-turning residence time was increased(P＜0.01),the positive expression of TH in brain nigrostriatal neuronal cells was increased,the structural morphology of the mitochondria was improved,and the expression of NCOA4,Fe2+,ACSL4,and LPCAT3 in BSHXG three dose groups were decreased(P＜0.05,P＜0.01),and the expression of FTH1 in BSHXG medium-and high-dose groups was increased(P＜0.05,P＜0.01),the expression of T-SOD and GSH in the Medopar and BSHXG three dose groups were increased(P＜0.01,P＜0.05).Conclusion:BSHXG ameliorates DA ergic neuronal injury by regulating NCOA4-mediated ferritinophagy and inhibiting ferroptosis in brain nigrostriatal neuronal cells.
NETL
NSTL
万方数据
