Neuroprotective effect of lipoic acid on SIRT1/P53 pathway in animal models of Parkinson's disease

Zhu Yanxia; Zhen Ning; Lv Dongfang; Liu Jiuzhi; Wang Xueli

doi:10.11850/j.issn.1009-122X.2023.12.040

Abstract：Objective To study the neuroprotective effect of lipoic acid regulating silent information regulator 1(SIRT1)/P53 pathway on Parkinson's disease(PD)animal models.Methods Forty-five male C517BL/6J mice were randomly divided into three groups:control group,model group and lipoic acid group.Both the model group and the lipoic acid group were induced to establish PD mouse models by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).The lipoic acid group was given intraperitoneal injection of lipoic acid,the model group and control group were intraperitoneally injected with an equal volume of normal saline.The ultrastructure of the midbrain neurons in the three groups of mice was observed under electron microscope,and the effect of lipoic acid on motor deficits in Parkinson's mice was evaluated by rope test,open field test and rotarod test.The apoptosis of dopaminergic neurons in the striatum and the expression levels of DA and DOPAC were evaluated.Western blotting was used to detect the expression of SIRT1/P53 pathway-related proteins.Results There were statistically significant differences in the total moving distance,average moving speed,hanging wire test score and falling latency of the three groups of mice(P<0.05).The score was higher than that of the model group and lower than that of the control group,while the fall latency was higher than that of the control group and lower than that of the model group(P<0.05).There were statistically significant differences in the neuron apoptosis rate in the brain tissue of the three groups of mice(P<0.05).The neuron apoptosis rate in the lipoic acid group was significantly lower than that in the model group and higher than that in the control group(P<0.05).There were statistically significant differences in the expression levels of DA,DOPAC,SIRT1 and P53 in the striatum of the three groups of mice(P<0.05),and the expression levels of DA,DOPAC and SIRT1 in the lipoic acid group were significantly higher than those in the model group and lower than those in the control group(P<0.05),while the expression level of P53 was lower than that of the model group and higher than that of the control group(P<0.05).Conclusions Lipoic acid can reduce the apoptosis of neurons in Parkinson's disease animal model mice,thereby exerting neuroprotective effect,and its mechanism may be related to the up-regulation of SIRT1/P53 pathway.