玄参对脾虚水湿不化大鼠模型的影响及其肝脏代谢组学分析

目的:探索玄参对脾虚水湿不化大鼠模型的影响,并利用代谢组学方法对生物标志物和代谢通路进行分析。方法:高脂低蛋白饲料喂养加尾部负重游泳的方法建立脾虚水湿不化大鼠模型,玄参水煎液高、低剂量给药2周后检测各给药组肝脏指数、血清蛋白、血脂、胃肠功能和水负荷的变化情况,给药剂量分别为1.35,5.40 g·kg-1。利用UPLC-Q-TOF-MS检测肝组织中内源性小分子代谢物,电喷雾正离子模式(ESI+)和负离子模式(ESI-)对样品进行检测,m/z 100~1 500;利用主成分分析(PCA)和偏最小二乘法-判别分析(PLS-DA)比较空白组、模型组,玄参高、低剂量组内源性小分子代谢物的变化情况;对差异代谢物进行京都基因与基因组百科全书(KEGG)代谢通路分析。结果:与模型组比较,玄参高剂量组的胃排空率和D-木糖排泄率显著升高;玄参低剂量组能升高血清白蛋白、总蛋白含量;玄参高剂量组能降低总胆固醇、低密度脂蛋白胆固醇含量和水负荷指数。代谢组学方法共鉴定出21个生物标志物,找到7条主要代谢通路,主要涉及胰岛素分泌、甘油磷脂代谢、嘌呤代谢、胆汁酸分泌、磷脂酶D信号通路、糖基磷脂酰肌醇锚的合成、内源性大麻素的生物合成等。结论:玄参对脾虚水湿不化模型大鼠的影响与改善消化功能、抑制糖代谢、改善血脂代谢等有关。

Effect of Scrophulariae Radix on Rat Model with Dampness Stagnancy due to Spleen Deficiency and Analysis of Its Liver Metabonomics

Objective: To explore the effect of Scrophulariae Radix on rat model with dampness stagnancy due to spleen deficiency,and to analyze biomarkers and metabolic pathways based on liver metabonomics. Method: The high fat and low protein diet plus swimming for 8 weeks under weight bearing condition was adopted to establish rat model with dampness stagnancy due to spleen deficiency.Liver index,serum albumin,blood fat,gastrointestinal function and water load were measured at 2 weeks after administration of high(5.40 g · kg^-1) and low(1.35 g · kg^-1) dose of Scrophulariae Radix decoction.UPLC-Q-TOF-MS was employed to analyze metabolites in liver tissue under electrospray ionization positive and negative ion mode with m/z 100-1 500.Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were adopted to compare the differential metabolites among the normal group,the model group,the high and low dose group of Scrophulariae Radix decoction;these different metabolites among four groups were analyzed by KEGG metabolic pathway method. Result: Compared with the model group,gastric emptying rate and D-xylose excretory rate in the high dose group were increased significantly;contents of serum albumin and total protein in the low dose group were increased;contents of low density lipoprotein-cholesterol,total cholesterol and water load index in the high dose group were decreased.A total of 21 biomarkers were identified and 7 major metabolic pathways were found,which mainly related to the insulin secretion,purine metabolism,bile acid secretion and so on. Conclusion: Treatment of Scrophulariae Radix on rat model with dampness stagnancy due to spleen deficiency is connected with improving the digestive function,inhibition of glucose metabolism,improving blood lipid metabolism and so on.