Study On The Positive Effect Of Kinetin On The AD Mice Model Induced By AlCl₃ And D-galactose

Objective: Oxidative stress is an important factor in the development of degenerative lesions in the brain of patients with Alzheimer’s disease.AlCl₃ and D-galactose which are used together to make AD mouse model can induce oxidative stress in the brain of mice and impair spatial cognitive ability of mice.It is known that kinetin has the properties of anti-oxidative damage and anti-aging,but it is not known whether kinetin can play a role in inhibiting oxidative stress in the brain.The aim of this study is to investigate whether kinetin has a positive effect on the AD mouse model induced by AlCl₃ and D-galactose.Methods:（1）Preparation of mouse AD model and kinetin intervention: AD mouse model was prepared by AlCl₃ and D-galactose in combination,and at the same time intervention was carried out with different concentrations of kinetin.Blank control group and only kinetin-excited group were also set.（2）The study of spatial memory ability of mice: water maze was uesd to evaluate the memory and cognitive ability of mice in each group.（3）Observation of histopathological changes of brain in mice: Hippocampal CA3 region of each group of mice by making paraffin sections and HE staining.（4）The detection of mouse brain biochemical indicators: The content of ACh,SOD,CAT and GSH-Px and the activity of AChE were measured by kit method.The activity of HO-1 and the content of AGEs,8-ISO-PGF and 8-OHDG were measured by enzyme-linked immunosorbent assay kit.（5）The contents and distribution of Aβ1-42 in the brain of mice were detected by immunohistochemistry and western blot.Results:（1）The mice in the model group had the characteristics of slowness,coarse fur and physical weight loss.（2）In the navigation experiment and space exploration experiment,the escape latency of the kinetin intervention group was significantly shorter than that of the model group,and the time of stay in the target quadrant was significantly longer than that in the model group（3）The pathological changes of pyramidal cells in the hippocampal CA3 region of the model group were significantly serious,but the degree of lesion in the kinetin intervention group decreased markedly compared with the control group（P <0.05）.And the results showed kinetin dose-dependent characteristics.（4）The activities of AChE,SOD,CAT,GSH-Px and the content of ACh and HO-1 in the model group were decreased（P <0.05）.And the levels of oxidative damage markers AGEs,8-OHdG and 8-ISO-PGF in the model group were significantly higher in the model group（P <0.05）.（5）The distribution and content of Aβ1-42 in model group mice cerebral cortex and hippocampus were significantly increased,while the expression and distribution of Aβ1-42 in the intervention group decreased and showed concentration-dependent characteristics.Conclusion:（1）kinetin can partially restore the cognitive and memory impairment induced by AlCl₃ and D-galactose in mice.（2）Kinetics can partially alleviate lesion in the brain of mice induced by AlCl₃ and D-galactose.（3）Kinetin has a neuroprotective effect on AlCl₃ and D-galactose-treated mice,which can restore ACh content and inhibit AChE activity.（4）For AlCl₃ and D-galactose-treated mice,kinetin can increase its antioxidant enzyme activity,enhance the expression of HO-1,and reduce oxidative damage.（5）Kinetin can inhibit the expression of Aβ1-42 in the brain of AlCl₃ and D-galactose treated mice.In summary,it is presumed that kinetin has the potential to treat AD.