Improvement effect of ursolic acid on cognitive function in rats during the process of AlCl3-induced Alzheimer's disease
Objective To observe the improvement effect of intragastric administration of ursolic acid(UA)on cog-nitive function in rats during the process of Alzheimer's disease(AD)induced by aluminium trichloride(AlCl3)and to ex-plore its mechanism.Methods Twenty-four male Wistar rats were randomly divided into the blank group(n=6),UA group(n=6),AlCl3 group(n=6)and AlCl3+UA group(n=6),respectively.The rats in the blank group were given normal saline,the rats in the UA group were intragastrically administered AlCl3 to establish the AD models,and the rats in the Al-Cl3+UA group were intragastrically given UA during the process of AD induced by AlCl3.After stopping intragastric admin-istration for 5 d,the cognitive function of rats in each group was observed by Morris water maze test.The rats in each group were killed by decapitation after anesthesia,and the cerebral cortex and hippocampus were taken.The aluminum content in the cerebral cortex and hippocampus was determined by spectrophotometry,and the activity of acetylcholinase(AChE)in the cerebral cortex and hippocampus was detected by colorimetry.The activity of superoxide dismutase(SOD),catalase(CAT)and glutathione(GSH)in cerebral cortex and hippocampus was measured,and the activity of thiobarbituric acid re-actants(TBARS)was calculated.The relative expression levels of inflammatory factors TNF-α,IL-6,NF-κB and COX-2 mRNA in cerebral cortex and hippocampus were detected by real-time fluorescence quantitative PCR.Results Com-pared with the blank group and the UA group,the escape latency was longer and the stay time in the original platform quad-rant was shorter in the AlCl3 group(both P<0.05).Compared with the AlCl3 group,the escape latency was shorter and the stay time in the original platform quadrant was longer in the AlCl3+UA group(both P<0.05).The content of aluminum in cerebral cortex and hippocampus in the AlCl3 group was higher than that in the other groups(P<0.05).The activity of AChE in cerebral cortex and hippocampus in the AlCl3 group was higher than that in the other groups(P<0.05).The activ-ity of TBARS in cerebral cortex and hippocampus of AlCl3 group was higher than that of the other groups,while the activity of SOD,CAT and GSH was lower than that of the other groups(all P<0.05).The relative expression levels of inflammato-ry cytokines TNF-α,IL-6,NF-κB and COX-2 mRNA in cerebral cortex and hippocampus in the AlCl3 group were higher than those in the other groups(all P<0.05).Conclusion UA can improve the cognitive function of AlCl3-induced AD model rats,and its mechanism may be related to the decrease of aluminum content,AChE activity,oxidative stress level and the expression of inflammatory factors in cerebral cortex and hippocampus.