恒清Ⅱ号方对阿尔茨海默病小鼠认知功能和粪便代谢组学影响研究

Study on the effect of HengqingⅡdecoction on cognitive function and fecal metabolomics in Alzheimer’s disease mice

目的研究恒清Ⅱ号方对阿尔茨海默病(AD)小鼠认知功能和粪便代谢组学的影响。方法将45只APPswe/PS1dE9双转基因AD模型小鼠随机分为模型组、恒清低剂量组、恒清中剂量组、恒清高剂量组、安理申组,每组9只,同月龄C57BL/6J小鼠9只作为正常组。采用水迷宫对各组小鼠进行行为学测试,以代谢组学技术筛选AD小鼠粪便生物标记物,并分析其对应的代谢通路。结果与模型组和恒清低剂量组比较,恒清中剂量组、恒清高剂量组、安理申组小鼠的逃避潜伏期明显延长(P均<0.05),穿越平台次数明显减少(P均<0.05);与恒清中剂量组和安理申组比较,恒清高剂量组小鼠的逃避潜伏期明显延长(P均<0.05),穿越平台次数明显减少(P均<0.05)。与模型组和恒清低剂量组比较,恒清中剂量组、恒清高剂量组、安理申组的乳酸、焦谷氨酸、L-谷氨酸、乙酰肉碱、鞘胺醇、花生四烯酸、前列腺素E1、环磷酸腺苷含量均升高(P均<0.05),L-酪氨酸、L-色氨酸含量均降低(P均<0.05);与恒清中剂量组和安理申组比较,恒清高剂量组的乳酸、焦谷氨酸、L-谷氨酸、乙酰肉碱、鞘胺醇、花生四烯酸、前列腺素E1、环磷酸腺苷含量明显升高(P均<0.05),L-酪氨酸、L-色氨酸含量明显降低(P均<0.05)。结论恒清Ⅱ号方可以改善AD小鼠的认知功能,且量效关系呈正相关;恒清Ⅱ号方抗AD的相关代谢通路主要涉及氨基酸的生物合成和氨基酸代谢等途径。

Objective It is to study the effect of HengqingⅡdecoction on cognitive function and fecal metabolomics in Alzheimer’s disease(AD)mice.Methods Forty five APPswe/PS1dE9 double transgenic AD model mice were randomly divided into model group,low dose HengqingⅡdecoction group(HQ-L group),medium dose HengqingⅡdecoction group(HQ-M group),high dose HengqingⅡdecoction group(HQ-H group),Aricept group,9 mice in each group.9 C57BL/6J mice of the same age were selected as normal group.The cognitive function of the mice in each group was tested by Water maze test.Fecal biomarkers of AD mice were screened by metabolomics and their corresponding metabolic pathways were analyzed.Results Compared with the model group and HQ-L group,the escape latency of mice in the HQ-M group,HQ-H group,and Aricept group was significantly prolonged(all P<0.05),and the number of crossing platforms was significantly reduced(all P<0.05).Compared with the HQ-M group and the Aricept group,the escape latency of mice in the HQ-H group was significantly prolonged(all P<0.05),and the number of crossing platforms was significantly reduced(all P<0.05).Compared with the model group and HQ-L group,the contents of lactic acid,pyroglutamic acid,L-glutamic acid,acetylcarnitine,sphingosine,arachidonic acid,prostaglandin E1 and cyclic adenosine monophosphate were all increased in HQ-M group,HQ-H group,and Aricept group(all P<0.05),and the contents of L-tyrosine and L-tryptophan were all decreased(all P<0.05);compared with HQ-M group and Aricept group,the contents of lactic acid,pyroglutamic acid,L-glutamic acid,acetylcarnitine,sphingosine,arachidonic acid,prostaglandin E1,and cyclic adenosine monophosphate in the HQ-H group were significantly increased(all P<0.05),the content of L-tyrosine and L-tryptophan was significantly reduced(all P<0.05).Conclusion HengqingⅡdecoction can improve cognitive function of AD mice,whose dose-effect relationship is positive.The related metabolic pathways of HengqingⅡdecoction against AD mainly involve amino acid biosynthesis and amino acid metabolism.