痛泻要方对IBS模型血清内源性物质代谢干预的实验研究.docVIP

痛泻要方对IBS模型血清内源性物质代谢干预的实验研究 　　[摘要]通过代谢组学评价痛泻要方对肠易激综合征（irritable bowel syndrome，IBS）大鼠模型血清内源性物质代谢干预效应，寻找潜在的生物标志物并分析其代谢途径，探讨痛泻要方的作用机制及病证模型的证候本质。将40只Wistar大鼠复制为IBS模型，随机分为模型对照组和痛泻要方给药组4组，另设空白对照组10只。痛泻要方（低、中、高）组分别灌胃剂量为0.203，0.406，0.812 g?mL-1的痛泻要方，空白对照组及模型对照组给予等体积的生理盐水，每日1次，连续2周。各组大鼠于灌胃第0，15天采集血清，经处理后供UPLC-Q-TOF-MS进行代谢组学分析。鉴定出8个潜在生物标志物，分析出8条主要代谢通路，其与IBS疾病的神经递质代谢、炎性免疫、脑神经功能及能量代谢等有关，痛泻要方对IBS疾病的作用机制可能涉及血清素突触和色氨酸代谢、半胱氨酸和甲硫氨酸代谢、甘油磷脂代谢、烟酸和烟酰胺代谢等过程，其可能是IBS模型肝旺脾虚证的生物学基础。 　　[关键词] 痛泻要方； 肠易激综合征； 肝旺脾虚； 内源性代谢物； 代谢组学 　　[Abstract] To evaluate the effect of Tongxie Yaofang on cardiac endogenous metabolism in irritable bowel syndrome（IBS） rats by using metabolomics method， find its potential biomarkers， analyze the metabolic pathways， and explore the pharmacological effects， mechanisms of action and syndrome essence of syndrome model. Forty Wistar rats were used to establish IBS models， and then randomly divided into four groups： model control group and Tongxie Yaofang treatment groups （high， medium， low dose）. Another 10 rats were used as normal group. The rats in Tongxie Yaofang-treated（low， medium and high dose） groups were orally administrated with Tongxie Yaofang extracts once a day for 2 weeks， respondingly with the doses of 0.203，0.406，0.812 g?mL-1. The rats in normal group and model control group were given with equal volume of saline once a day for 2 weeks. On the 0 and 15th days， serum was collected and each sample extract was analyzed by UPLC-Q-TOF-MS. Eight potential biomarkers were identified and 8 major metabolic pathways were found to be related with IBS diseases neurotransmitter metabolism， inflammatory immunity， brain function and energy metabolism， etc. Tongxie Yaofang had certain pharmacological effects on IBS， and its mechanism may be related to serotonergic synapse， tryptophan metabolism， cysteine and methionine metabolism， glycerophospholipid metabolism， nicotinate and nicotinamide metabolism and so on， which might be the biological basis of IBS liver-spleen defic