基于代谢组学研究厚朴“发汗”前后对胃肠动力障碍大鼠的影响

基于代谢组学方法,对厚朴"发汗"前后治疗胃肠动力障碍大鼠的血清代谢物进行对比,研究厚朴"发汗"增效减毒的作用机制。采用L-精氨酸腹腔注射建立胃肠动力障碍大鼠模型,以大鼠胃内色素相对残留率和小肠推进比作为药效学指标,采用LC-MS的代谢组学技术,并结合主成分分析(PCA)、偏最小二乘判别分析(PLS-DA)和正交校正的偏最小二乘判别分析(OPLS-DA)等方法筛选并鉴定与胃肠动力障碍相关的生物标志物,利用MetPA数据库分析相关代谢通路。结果表明厚朴不管发汗与否,均能改善胃肠动力障碍,且"发汗"厚朴作用强于"未发汗"厚朴组。实验各组的代谢物能够显著区分,发现并初步鉴定了15个差异代谢物及17条相关通路。厚朴起效的机制可能是通过提高丙氨酸、天门冬氨酸和谷氨酸代谢通路中L-谷氨酸胺的含量,保护胃肠道屏障而改善胃肠动力障碍;厚朴"发汗"前通过牛磺酸和亚牛磺酸代谢,初级胆汁酸生物合成通路而降低牛磺酸,提高甘氨鹅脱氧胆酸含量,可能会加大肝肾损伤几率;而厚朴"发汗"后,通过提高色氨酸通路中L-色氨酸和5-羟色胺含量来进一步增强胃肠动力,并避免了有害代谢物产生从而达到增效减毒的作用。

Study on influence of Magnolia officinalis before and after "sweating" on gastrointestinal motility disorder in rats by metabolomics

Based on metabolomics,the effect of Magnolia officinalis before and after " sweating" on gastrointestinal motility disorder( rat) was compared. To study the mechanism of M. officinalis " sweating" increased the efficacy and reduced the toxicity. The rat model of gastrointestinal motility disorder was established by intraperitoneal injection of L-arginine. Pharmacodynamic indexes were relative residual rate of gastric pigment and intestinal propulsion ratio in rats. LC-MS metabolomics and multivariate statistical analysis were used to screen and identify biomarkers associated with gastrointestinal motility disorders,and MetPA database was used to analyze related metabolic pathways. The results showed that M. officinalis could improve gastrointestinal motility disorder whether it " sweating" or not,and the effect of " sweating" M. officinalis was stronger than that of " no sweating" M. officinalis. The metabolites of the experimental groups could be distinguished distinctly,and 15 different compounds and 17 related pathways were identified preliminarily. The mechanism of M. officinalis might be to improve gastrointestinal motility disorder by increasing the content of L-glutamate in the metabolic pathway of alanine,aspartate and glutamate and protecting gastrointestinal barrier. Before " sweating",M. officinalis could reduce taurine through metabolism of taurine and taurine and biosynthetic pathway of primary bile acid,increase the content of deoxycholic acid in glycine goose,and increase the risk of liver and kidney injury. After " sweating",M. officinalis could enhance gastrointestinal motility by increasing the contents of L-tryptophan and serotonin in the tryptophan pathway,and avoid the production of harmful metabolites to achieve synergistic and detoxifying effect.