基于血清代谢组学探讨香砂六君合半夏泻心汤治疗糖尿病胃轻瘫大鼠的作用机制  

Study on the Mechanism of Xiangsha Liujun Combined with Banxia Xiexin Decoction in Treating Diabetic Gastroparesis Rats Based on Serum Metabonomics

作　　者：崔国良 冯小可[1,2] 魏睦新[1,2] 蒋金桃 林贞妍 谢立群[1,2] CUI Guoliang;FENG Xiaoke;WEI Muxin;JIANG Jintao;LIN Zhenyan;XIE Liqun(The First Affiliated Hospital of Nanjing Medical University,Nanjing Jiangsu China 210029;Institute of Integration of Chinese and Western Medicine,Nanjing Medical University,Nanjing Jiangsu China 210029)

机构地区：[1]南京医科大学第一附属医院,江苏南京210029 [2]南京医科大学中西医结合研究所,江苏南京210029

出　　处：《中医学报》2021年第5期1035-1041,共7页Acta Chinese Medicine

基　　金：江苏省中医药科技项目(YB2017088);第四批全国中医(临床、基础)优秀人才研修项目{国中医药人教发[2017]24号}。

摘　　要：目的:采用血清代谢组学探讨香砂六君合半夏泻心汤治疗糖尿病胃轻瘫大鼠的作用机制。方法:除正常组外,其余大鼠给予腹腔注射链脲佐菌素及高脂饲料喂养建立糖尿病胃轻瘫大鼠模型。大鼠模型成功建立后随机分为模型组、莫沙比利组(1.56 mg·kg^(-1))及香砂六君合半夏泻心汤组(9.3 g·kg^(-1))。给予药物干预8周后,测定各组大鼠胃残留率;收集大鼠血清样本,采用GC-MS技术对血清样本进行高分辨质谱检测,应用PLS-DA多元模式进行血清代谢轮廓的比较以及生物标志物的鉴定,运用MetPa数据库分析相关代谢通路。结果:与正常组相比,模型组的胃残留率显著升高(P<0.01);香砂六君合半夏泻心汤组和莫沙必利组的胃残留率较模型组明显降低(P<0.05)。血清代谢组学结果显示:正常组和模型组的代谢轮廓具有明显的差异,香砂六君合半夏泻心汤组的代谢轮廓趋近正常组,并对血清中N-乙酰天门冬氨酸、葡萄糖-1-磷酸、塔格糖、3-6脱水-D-半乳糖、木糖醇和脯氨酸等13个生物标志物具有明显的回调作用,并筛选出2条相关的代谢通路。结论:香砂六君合半夏泻心汤对糖尿病胃轻瘫大鼠有一定改善胃动力作用,其作用机制可能与通过回调多种血清代谢产物的含量及调控多条代谢通路等相关。Objective:To explore the mechanism of Xiangsha Liujun combined with Banxia Xiexin Decoction in the treatment of diabetic gastroparesis rats by using serum metabonomics.Methods:Except for the normal group,the other rats were given intraperitoneal injection of streptozotocin and high-fat diet to establish a rat model of diabetic gastroparesis.After the successful establishment of the rat model,the rats were randomly divided into model group,mosapride group(1.56 mg·kg^(-1))and Xiangsha Liujun combined with Banxia Xiexin Decoction group(9.3 g·kg^(-1)),with 10 rats in each group.After 8 weeks of drug intervention,the gastric residue rate of rats in each group was determined;rat serum samples were collected,and the serum samples were detected by high-resolution mass spectrometry using GC-MS technology.The PLS-DA multivariate model was used to compare serum metabolic profiles and biological.For the identification of markers,the MetPa database was used to analyze related metabolic pathways.Results:Compared with the normal group,the gastric residue rate of the model group was significantly increased(P<0.01);the gastric residue rate of Xiangsha Liujun combined with Banxia Xiexin Decoction group and mosapride group was significantly lower than that of the model group(P<0.05).The results of serum metabolomics showed that the metabolic profile of the normal group and the model group was significantly different.The metabolic profile of Xiangsha Liujun combined with Banxia Xiexin Decoction group approached the normal group,and had obvious callback effects of the serum levels in 13 biomarkers,such as N-acetylaspartic acid,glucose-1-phosphate,tagatose,3-6 dehydrated-D-galactose,xylitol and proline.2 related metabolic pathways had been screened out.Conclusion:Xiangsha Liujun combined with Banxia Xiexin Decoction has a certain effect on improving gastric motility in diabetic gastroparesis rats,and its mechanism of action may be related to the adjustment of the content of various serum metabolites and the regulation of multiple me

关 键 词：香砂六君合半夏泻心汤 代谢组学 糖尿病胃轻瘫 生物标记物 代谢通路 

分 类 号：R285.5[医药卫生—中药学]