Effects of Zexie Decoction(泽泻汤)on Cognitive Function and Neuroinflammation of Brain Tissue in Mouse Models with High-Calorie Diet-Induced Cognitive Impairment
Objective To investigate the mechanism of Zexie Decoction(泽泻汤)in inhibiting neuroinflamma-tion and improving cognitive impairment mediated by high-calorie diet.Methods Twenty seven C57BL/J mice were randomly divided into control group(n=9),model group(n=9)and Zexie Decoction group(n=9).The mice in the model group and the Zexie Decoction group were fed with high-calorie diet to establish the model of cognitive im-pairment.Meanwhile,the mice in Zexie Decoction group were also fed with 0.36 g/(kg·d)Zexie Decoction,and the mice in the control group and model group were fed with the same volume of normal saline for 8 weeks.The body weight of mice was recorded at the same time every week;after intervention,oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)commenced;the cognitive level of mice was detected by Morris water maze,open field test,new object recognition test and Y maze;magnetic resonance spectroscopy(MRS)was used to detect the expression of N-acetylaspartate(NAA),choline(CHO),lactic acid(Lac),creatine(Cr),lipid(Lip),and myoInositol(mI)in left hippocampus,hypothalamus and cortex.Western blotting was used to detect the expression of synaptophysin(SYN),synaptosome associated protein-25(SNAP-25),postsynaptic dense protein-95(PSD-95),tumor necrosis factor-α(TNF-α),nuclear factor kappa B(NF-κB p65)and its phosphorylated form(P-NF-B p65)in mouse brain;Nissl's staining was used to detect the morphological changes of hippocampal neurons.Results Com-pared with the control group,body mass,blood glucose in oral glucose tolerance test,and blood glucose in insulin tolerance test increased in the model group;in the Morris water maze experiment,the total distance travelled and es-cape latency of the model group mice increased,the time spent in the platform area and the number of times traversing the platform decreased on days 3 and 4;in the open-field experiment,the number of times the model group mice entered the central area,the ratio of the time in the central area to the total time,and the ratio of the distance trav-elled in the central area to the total distance significantly decreased;in the new object recognition test,the frequency of new object recognition and recognition index were significantly lower in the model group mice;in the Y-maze test,the spontaneous alternation rate of mice in the model group was significantly lower(P＜0.05 or P＜0.01);in the left hip-pocampus,hypothalamus,and cortex of mice in the model group,the CHO/Cr,NAA/Cr significantly decreased,and the mI/Cr,Lac/Cr and Lip/Cr significantly increased;SYN/β-actin,SNAP-25/β-actin and PSD-95/β-actin values sig-nificantly decreased,and p-NF-KB p65/NF-κB p65 and TNF-α/β-actin values significantly increased in brain tissue(P＜0.05 or P＜0.01).Compared with the model group,the above indexes of mice in the Zexie Decoction group sig-nificantly improved(P＜0.05 or P＜0.01).The results of Nissl staining showed that compared with the control group,the neurons in the dentate gyrus of the hippocampus in the model group were scattered and sparsely arranged,the density was significantly reduced,the nuclei of the cells had consolidation and shrinkage,the number of Nissl vesicles was reduced,and the staining became lighter;compared with the model group,the density of neurons in the hippo-campal dentate gyrus region of the Zexie Decoction group increased,the wrinkling of nuclei improved,the cell gap narrowed,and the arrangement was slightly tight.Concusion The ameliorative effect of Zexie Decoction on cognitive function in mice with high-calorie diet-induced cognitive impairment may relate to the restructuring of glucose metabo-lism homeostasis,inhibition of neuroinflammation,reduction of neuronal damage,and enhancement of synaptic plasticity.
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