| 张悦,程苇钇,何莉,任玮晔,朴寄纲,包丹丹.基于代谢组学探讨大黄-附子药对治疗阳虚便秘证的药物配伍机制[J].浙江中西医结合杂志,2024,34(10): |
| 基于代谢组学探讨大黄-附子药对治疗阳虚便秘证的药物配伍机制 |
| Study of the Compatibility Mechanism of Rhei Radix et Rhizoma and Aconiti Lateralis of Yang Deficiency Constipation Based on MetabonomicsZHANG Yue1, CHENG Wei-yi3, HE Li3, REN Wei-ye3, PIAO Ji-gang3*, BAO Dan-dan2* |
| 投稿时间：2024-03-06 修订日期：2024-09-22 |
| DOI： |
| 中文关键词: 阳虚便秘 大黄 附子 配伍机制 代谢组学 |
| 英文关键词:yang deficiency constipation Rhei Radix et Rhizoma Aconiti Lateralis compatibility mechanism metabonomics |
| 基金项目:浙江省中医药科技计划项目青年人才基金项目（No.2021ZQ036） |
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| 中文摘要: |
| 目的 结合代谢组学技术观察大黄-附子药对治疗阳虚便秘证效果，探讨其机制和关键代谢通路。方法 将40只大鼠随机分为空白对照组、模型对照组、大黄单煎组、附子单煎组、大黄-附子合煎组，每组8只。除空白对照组外，其余各组建立阳虚便秘证大鼠模型。空白对照组和模型对照组予以煮沸后的超纯水按1 mL/200 g的剂量灌胃，大黄单煎组予以大黄单煎液按1 mL/200 g的剂量灌胃，附子单煎组予以附子单煎液按1 mL/200 g的剂量灌胃，大黄附子合煎组予以大黄附子合煎液按1 mL/200 g的剂量灌胃，共计给药4 d。观察大黄、附子单煎液及合煎液对阳虚便秘证大鼠模型的体温、小肠推进率等的影响；测定阳虚便秘证大鼠血中胃动素（MTL）；取小肠组织于显微镜下观察肠壁病理改变；同时基于液相色谱-质谱联用技术对大鼠代谢产物进行模式识别与分析，鉴定差异代谢物并分析其富集的代谢通路。结果 大黄-附子合煎组大鼠在给药4次后，与模型对照组比较，大鼠肛温[(38.17±0.60) ℃比(36.07±0.25) ℃，P<0.05]、额温[(35.77±0.06) ℃比(35.27±0.15) ℃，P<0.01]、小肠推进率[(73.58±2.47)%比(43.56±2.79)%，P<0.01]、MTL值[(350.96±15.91) pg/mL比(280.97±25.13) pg/mL，P<0.05]明显升高，差异有统计学意义；代谢组学结果方面，在大黄-附子药对干预前后大鼠代谢谱明显分离，最终筛选出尿嘧啶、牛磺酸、磷酸胆碱、三甲胺、2-羟基丁酸、丙酸、乙醇、色氨酸、肌氨酸、异丁酸盐、甘氨酸11种内源性差异代谢物，主要富集于苯丙氨酸、酪氨酸和色氨酸的生物合成三条代谢通路。结论 大黄-附子药对配伍后对阳虚便秘证动物有确切疗效，不但能上调胃肠激素，还能通过影响甘氨酸、丝氨酸和苏氨酸、苯丙氨酸、酪氨酸和色氨酸的生物合成代谢通路治疗阳虚便秘证。 |
| 英文摘要: |
| OBJECTIVE This study aims to observe the therapeutic effect of rhubarb aconite combination on Yang deficiency constipation syndrome using metabolomics techniques to explore its mechanism and key metabolic pathways. METHODS Forty rats were randomly divided into blank control group, model control group, rhubarb single decoction group, aconite single decoction group, and rhubarb aconite combined decoction group, with 8 rats in each group. Except for the blank control group, other groups were established with rat models of Yang deficiency constipation syndrome. The blank control group and model control group were given boiled ultrapure water by gavage at a dose of 1 mL/200 g, the rhubarb single decoction group was given rhubarb single decoction by gavage at a dose of 1 mL/200 g, the aconite single decoction group was given aconite single decoction by gavage at a dose of 1 mL/200 g, and the rhubarb aconite combined decoction group was given rhubarb aconite combined decoction by gavage at a dose of 1 mL/200 g, for a total of 4 days of administration. Observing the effects of single and combined decoction of rhubarb and aconite on body temperature and small intestine propulsion rate in a rat model of Yang deficiency constipation syndrome; Measure the levels of motilin (MTL) in the blood of rats with Yang deficiency constipation syndrome; Take small intestine tissue and observe pathological changes in the intestinal wall under a microscope; At the same time, pattern recognition and analysis of rat metabolites were carried out based on liquid chromatography-mass spectrometry technology, identifying differential metabolites and analyzing their enriched metabolic pathways. RESULTS After 4 doses of rhubarb aconite decoction, compared with the model control group, rats in the rhubarb aconite decoction group showed significant increases in anal temperature [(38.17±0.60) ℃ vs. (36.07±0.25) ℃, P<0.05], frontal temperature [(35.77±0.06) ℃ vs. (35.27±0.15) ℃, P<0.01], intestinal propulsion rate [(73.58±2.47)% vs. (43.56±2.79)%, P<0.01], and MTL [(350.96±15.91) pg/mL vs. (280.97±25.13) pg/mL, P<0.05], with statistically significant differences; In terms of metabolomics results, the metabolic profiles of rats before and after intervention with rhubarb aconite were significantly separated. Finally, 11 endogenous differential metabolites were screened, including uracil, taurine, choline phosphate, trimethylamine, 2-hydroxybutyric acid, propionic acid, ethanol, tryptophan, creatine, isobutyrate, and glycine, mainly enriched in the biosynthesis pathways of phenylalanine, tyrosine, and tryptophan. CONCLUSION The combination of rhubarb and aconite has a definite therapeutic effect on animals with Yang deficiency constipation syndrome. It can not only up-regulate gastrointestinal hormones, but also treat Yang deficiency constipation by affecting the bioanabolic pathways of glycine, serine and threonine, phenylalanine, tyrosine and tryptophan. |
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