痛泻要方对IBS模型血清内源性物质代谢干预的实验研究(1)
[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
, 百拇医药
[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 deficiency syndrome.
, 百拇医药
[Key words] Tongxie Yaofang； IBS； liver stagnation and spleen deficiency； endogenous metabolites； metabolomics
本研究組在前期工作中已进行了较深入的痛泻要方对肠易激综合征(irritable bowel syndrome，IBS)大鼠模型脑-肠互动效应机制影响的研究[1-2]，并对其作用机制有一定阐释。对机体、病证的作用机制仅通过某些作用靶点、机制、通路来阐释机体证候复杂性、方药成分有效性的研究模式，是不能完全将药物对病证的作用机制阐明清楚。而如何全面、系统的阐明方药对病证整体效应，值得思考。代谢组学通过机体内小分子代谢产物整体变化规律，还原相关联的生物事件，以揭示机体的生物状态实质和药物作用机制[3]。代谢组学具有整体动态、综合与分析等系统方法学特点，有与中医治疗疾病的整体观念相近的特点[4]。方药则可对机体代谢途径中某些环节作用特异性强，干预其代谢产物及代谢网络[5]。通过代谢组学与中医方证相结合，从体内代谢产物的角度明晰方药代谢网络干预效应，而明确对动物模型的作用机制及实质。因此，本实验将IBS病证结合模型和代表方药——痛泻要方作为有机系统进行研究，通过痛泻要方对IBS动物模型血清内源性代谢物干预效应的评价，研究其对IBS病证模型调控差异、调控效应，发掘出其生物标记物，建立其代谢模式特征，通过基于体内作用的物质质量变化规律以探求痛泻要方的作用本质及所适应病证模型的证候本质。, 百拇医药(历凯 匡海学 殷越 张洁玉 王智 张秋樾 旺建伟)
[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
, 百拇医药
[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 deficiency syndrome.
, 百拇医药
[Key words] Tongxie Yaofang； IBS； liver stagnation and spleen deficiency； endogenous metabolites； metabolomics
本研究組在前期工作中已进行了较深入的痛泻要方对肠易激综合征(irritable bowel syndrome，IBS)大鼠模型脑-肠互动效应机制影响的研究[1-2]，并对其作用机制有一定阐释。对机体、病证的作用机制仅通过某些作用靶点、机制、通路来阐释机体证候复杂性、方药成分有效性的研究模式，是不能完全将药物对病证的作用机制阐明清楚。而如何全面、系统的阐明方药对病证整体效应，值得思考。代谢组学通过机体内小分子代谢产物整体变化规律，还原相关联的生物事件，以揭示机体的生物状态实质和药物作用机制[3]。代谢组学具有整体动态、综合与分析等系统方法学特点，有与中医治疗疾病的整体观念相近的特点[4]。方药则可对机体代谢途径中某些环节作用特异性强，干预其代谢产物及代谢网络[5]。通过代谢组学与中医方证相结合，从体内代谢产物的角度明晰方药代谢网络干预效应，而明确对动物模型的作用机制及实质。因此，本实验将IBS病证结合模型和代表方药——痛泻要方作为有机系统进行研究，通过痛泻要方对IBS动物模型血清内源性代谢物干预效应的评价，研究其对IBS病证模型调控差异、调控效应，发掘出其生物标记物，建立其代谢模式特征，通过基于体内作用的物质质量变化规律以探求痛泻要方的作用本质及所适应病证模型的证候本质。, 百拇医药(历凯 匡海学 殷越 张洁玉 王智 张秋樾 旺建伟)