开心散改善小鼠肥胖相关认知障碍的机制研究

Mechanism Study on Kaixin Powder Improving Obesity Related Cognitive Disorders in Mice

目的 观察开心散对肥胖相关认知障碍模型小鼠认知下降的改善作用,并探究其作用机制。方法 6周龄C57BL/6J雄性小鼠随机分为普通饮食、高脂饮食、开心散低剂量和开心散高剂量组各10只。通过长期(16周)高脂饮食方法复制肥胖相关认知障碍动物模型,造模13~16周期间,各组小鼠灌胃相应药物。16周后,应用Morris水迷宫评价各组小鼠的认知功能;ELISA法测定海马区白细胞介素(interleukin,IL)-6、肿瘤坏死因子(tumor necrosis factor,TNF)-α、IL-10及转化生长因子(transforming growth factor,TGF)β1浓度;免疫荧光法标记海马区M1型、M2型小胶质细胞;Western blot法测定海马区精氨酸酶(arginase,Arg)-1蛋白表达。结果 与普通饮食组小鼠比较,高脂饮食组小鼠体质量明显增加,逃避潜伏期明显延长,穿越平台区次数及平台区象限探索时间明显减少,海马区IL-6、TNF-α含量及M1型小胶质细胞明显增多(P<0.01),IL-10、TGF-β1、Arg-1含量及M2型小胶质细胞显著减少(P<0.01)。与高脂饮食组比较,开心散干预组小鼠体质量下降、认知功能明显改善,海马区IL-6、TNF-α含量及M1型小胶质细胞明显减少(P<0.05),IL-10、TGF-β1、Arg-1含量及M2型小胶质细胞显著增加(P<0.05),且开心散的干预作用呈现剂量依赖性。结论 开心散可通过减轻体质量及调控海马区小胶质细胞转化向M2型倾斜降低海马区炎症因子水平,进而改善高脂饮食诱导的肥胖相关认知障碍。

Objective To observe the improvement effect of Kaixin powder on cognitive decline in mice with obesity-related cognitive impairment model,and explore its mechanism.Methods Six-week-old C57BL/6J male mice were randomly divided into a normal diet,high-fat diet,Kaixin powder low-dose,and Kaixin powder high-dose group(10 mice in each group).The animal model of obesity-associated cognitive impairment was established by a long-term(16-week)high-fat diet,and the mice in each group were gavaged with the corresponding drugs during week 13~16 of modeling.16 weeks later,the cognitive function of mice in each group was evaluated by the Morris water maze method.After behavioral experiments,the concentrations of interleukin(IL)-6,tumor necrosis factor(TNF)-α,IL-10,and transforming growth factor(TGF)-β1 in the hippocampus were measured by ELISA.M1 and M2 microglia in the hippocampus were detected by immunofluorescence.The protein expression of Arg-1 in the hippocampus was measured by Western blot.Results Compared with normal diet mice,mice in the high-fat diet group showed a significant increase in body mass,a significant prolongation of escape latency,a significant decrease in the number of traversals across the plateau area and the exploration time of the plateau quadrant,a significant increase in the content of IL-6,TNF-αand M1 microglia in the hippocampus(P<0.01),and a significant decrease in the content of IL-10,TGF-β1,Arg-1 and M2 type microglia(P<0.01).Compared with the high-fat diet group,the mice in the Kaixin powder intervention group had decreased body mass,significantly improved cognitive function,significantly decreased IL-6,TNF-αand M1 microglia(P<0.05),and significantly increased IL-10,TGF-β1,Arg-1,and M2 microglia in the hippocampus(P<0.05).The intervention effect of Kaixin powder showed a dose-dependent effect.Conclusion Kaixin powder can reduce the level of inflammatory factors in the hippocampus by reducing body mass and regulating the conversion of microglia to M2-type in the hippocampus,and then improve the high-fat diet-induced obesity-related cognitive impairment.