中國全科醫學-2024年1月 第27卷 第2期

【Abstract】 Background Alzheimer's disease（AD）is a common and irreversible neurodegenerative brain disease 
that severely affects the quality of life and survival of patients，while there is still a lack of effective treatments to delay or stop 
disease progression. Traditional Chinese medicine（TCM） and its active ingredients have important potential in the prevention 
and treatment of AD. Objective To investigate the effects of poric acid（PA）on cognitive impairment and nuclear factor E2-
related factor 2（Nrf2）/solute carrier family 7A11（SLC7A11）/glutathione peroxidase 4（GPX4）signaling pathway in AD 
rats. Methods Seventy-five male SPF grade SD rats aged 6 to 8 weeks were divided into the control group（Control group），
AD Model group（Model group），PA treatment group （PA group） and PA+Nrf2 inhibitor group（PA+ML385 group）by 
random number table method to prepare AD rat model from January to September，2022. After successful modeling 50 mg/kg 
PA was intraperitoneally injected into the PA group，50 mg/kg PA and 30 mg/kg ML385 was intraperitoneally injected into the 
PA+ML385 group，and 0.9% sodium chloride solution was intraperitoneally injected into the Control group and Model group. The 
Morris water maze experiment was performed 24 h after the last dose，and the positioning navigation experiment was carried out on 
days 2，4 and 6 to record the time when the rats arrived at the platform（escape latency）. The platform was removed on day 7，
and the duration of the rats staying on the platform and the number of times they crossed the platform within 120 s were recorded. 
The pathological changes of hippocampal neurons in each group were observed after Nissl staining. Iron deposition was detected 
by Prussian blue staining，GPX4 expression and GSH，MDA and Fe2+ contents were detected by immunofluorescence staining. 
The protein expression levels of Nrf2，SLC7A11 and GPX4 in rat hippocampus were detected by Western blotting. Results The 
escape latency of the Model group was higher than that of the Control group and PA group，and escape latency of the PA+ML385 
group was higher than that of the PA group at 2，4 and 6 days after the last administration. The platform residence time and 
platform crossing times in the Model group were lower than those in the Control group and PA group，and those in the PA+ML385 
group were lower than those in PA group，and the difference was statistically significant （P<0.05）. The results of Nissl staining 
showed severe neuronal necrosis，nucleus shrinkage and decreased number of Nissl bodies in the Model group， decreased 
neuronal necrosis with tight arrangement and increased number of Nissl bodies in the PA group，significantly increased neuronal 
damage and decreased the number of Nissl bodies in the PA+ML385 group. The Prussian blue staining results showed that iron 
deposition in the Model group was higher than that in the Control group，iron deposition in the PA group was lower than that in 
the Model group，and iron deposition in the PA+ML385 was higher than that in the PA group. The results of immunofluorescence 
staining showed that green fluorescence was weakened and GPX4 positive cells were reduced in the Model group，green 
fluorescence was enhanced and GPX4 positive cells were increased in the PA group compared with the Model group，and GPX4 
positive cells were decreased in the PA+ML385 group compared with the PA group. GSH in the Model group was lower than that in 
the Control group and PA group，GSH in the PA+ML385 group was lower than that in the PA group. MDA and Fe2+ in the Model 
group were higher than those in the Control group and PA group，and those in the PA+ML385 group were higher that the PA 
group，and the differences were statistically significant （P<0.05）. The relative expression levels of Nrf2，SLC7A11 and GPX4 
in the Model group were lower than those in the Control group and PA group，and those in the PA+ML385 group were lower than 
those in the PA group，and the differences were statistically significant （P<0.05）. Conclusion　PA can improve the cognitive 
impairment of AD rats，and its mechanism may be related to the inhibition of iron death by activating Nrf2/SLC7A11/GPX4 signal 
pathway.

本研究中產品：茯苓酸（PA），購自四川恒誠致遠生物科技有限公司（Naturewill biotechnology Co., Ltd.）