香砂六君合半夏泻心汤治疗糖尿病胃轻瘫大鼠的尿液代谢组学研究

Urinary Metabonomics Research of Xiangsha Liujun combined with Banxia Xiexin Decoction in Rats with Diabetic Gastroparesis Treated

目的:探讨香砂六君合半夏泻心汤对糖尿病胃轻瘫大鼠尿液中内源性代谢产物的影响,利用尿液代谢组学分析其可能的作用机制。方法:采用腹腔注射80 mg/kg链脲佐菌素联合不规则饮食以制备糖尿病胃轻瘫模型,造模成功后,随机分为模型对照组、莫沙比利1.56 mg/kg组、香砂六君合半夏泻心汤9.3 g/kg组,每组6只;另设6只健康SD大鼠为正常对照组。灌胃给药干预8 w后,测定各组大鼠胃排空率和小肠推进率,利用代谢笼收集24 h尿液,通过气相色谱与质谱联用(GS-MS)技术检测尿液样品,应用主成分分析(PCA)和偏最小二乘法-判别分析(PLS-DA)进行代谢轮廓的比较以及生物标志物的鉴定,利用MetPa数据库分析相关代谢通路。结果:与正常对照组比较,模型对照组胃排空率和小肠推进率显著降低(P<0.01),其尿液代谢轮廓发生明显变化。与模型对照组比较,莫沙比利1.56 mg/kg、香砂六君合半夏泻心汤9.3 g/kg组胃排空率明显升高(P<0.05),其尿液代谢轮廓能明显区分且趋近正常对照组。香砂六君合半夏泻心汤9.3 g/kg干预治疗后对β-丙氨酸、葡萄糖酸内酯、苯甲酸、3-(3-羟基苯基)-丙酸、糖二酸、异麦芽酮糖醇、核糖醇、苏氨酸、肌酸、丝氨酸、苯乙酸、对苯二酚、甲基乙内酰脲这13个代谢产物的含量具有一定的回调作用,并作用于3条代谢通路。结论:香砂六君合半夏泻心汤可促进糖尿病胃轻瘫大鼠的胃排空,其作用机制可能与改善尿液中代谢产物的含量异常有关。

Objective:To explore the effect of Xiangsha Liujun and Banxia Xiexin Decoction on the endogenous metabolites in the urine of diabetic gastroparesis rats,and to analyze its possible mechanism by urine metabolomics.Methods:SD rats were given irregular high-fat diet combined with intraperitoneal injection 80 mg/kg streptozotocin to establish the diabetic gastroparesis model.After modeling,rats were randomly divided into the model group,Mosapride group(1.56 mg/kg)and Xiangsha Liujun and Banxia Xiexin Decoction group(9.3 g/kg),6 rats in each group.And 6 healthy rats were set as the control group.After 8 weeks administration,the gastric emptying rate and small intestinal propulsion rate were measured.Urine was collected for 24 hours by the metabolic cage,the rat urine in each group was detected by GC-MS.PCA and PLS-DA multivariate model was used to compare the differences of the serum metabolic profiles and identify potential biomarkers.MetPa database was used to analyze relevant metabolic pathway.Results:Compared with the control group,the gastric emptying rate and small intestine propulsion rate in the model group were significantly reduced(P<0.01),and the urine metabolic profile was significantly different.Compared with the model group,the gastric emptying rates in Xiangsha Liujun and Banxia Xiexin Decoction groups were increased(P<0.05),and the urine metabolic profiles in Xiangsha Liujun and Banxia Xiexin Decoction groups were significantly different and close to that in the control group.After treatment wth Xiangsha Liujun and Banxia Xiexin Decoction,the contents of 13 metabolites:beta-alanine,gluconic acid lactone,benzoic acid,3-(3-hydroxyphenyl)-propionic acid,hydroquinone,saccharic acid,1-methylhydantoin,palatinitol,ribitol,threonine,creatine,serine,phenylacetic acid were recoveried,while the drug also acted on 3 metabolic pathway.Conclusion:Xiangsha Liujun and Banxia Xiexintang has a certain promoting effect on gastric emptying in DGP rats,and its mechanism may be related to the improvement of the content disorder of metabolites in urine.