| Hawthorn leaves have the effect of promoting blood circulation,which helps in removing blood stasis,regulating qi,reducing turbidity and lowering blood fat.It is comprehensively utilized for the stagnation of qi and blood stasis,chest pain and hyperlipidemia.Its main active ingredient is flavonoids.In this dissertation,the rat model of glycolipid metabolism disorder was used to investigate the pharmacokinetic of hawthorn leaf total flavonoids(HLF)and Vitexin-2''-O-rhamnoside(RHV)and their effects on endogenous substance metabolism.The research contents are as follows:1.Glycolipid metabolism disorder rats were created by high-sugar and high-fat diet and combined with intraperitoneal injection of streptozotocin.A HPLC-UV method for the determination of RHV and its main metabolite vitexin(VIT)in the plasma of model rats was established.After the RHV was administered to rats,the prototypical medicine and metabolites in plasma were analyzed to obtain pharmacokinetic parameters of RHV and VIT.2.High performance liquid chromatography-quadrupole time-of-flight mass spectrometry(HPLC-Q-TOF-MS)analysis method was established for the determination of endogenous substances in rats' blood samples.The endogenous substances in the rats' serum were analyzed after single-time medicine administration and multiple-time medicine administrations,and 24 endogenous substances were found to have changed significantly,of which the content of phenylalanine,tryptophan,leucine and pyruvic acid decreased;the content of arachidonic acid,stearic acid,cholalic acid and oleinic acid increased.HLF and RHV can reverse the abnormal changes of these substances and they might affect fatty acid metabolism,amino acid metabolism,and TCA cycle.3.HPLC-Q-TOF-MS analysis method was established for the endogenous substances in rat urine samples.The endogenous substances in rats' urine samples before and after the administration of HLF or RHV were analyzed,and 25 endogenous substances were found to have changed significantly,which turned out the content of lactic acid,citric acid,hippuric acid and alanine decreased,and the content of chenodeoxycholic acid,glycocholic acid and uric acid increased.HLF and RHV can reverse the abnormal changes mentionedabove,and they might affect bile acid metabolism and TCA cycle.4.HPLC-Q-TOF-MS analysis method was established for the endogenous substances in rats' fecal samples.The endogenous substances in the feces of rats with glycolipid metabolism disorder were analyzed respectively before and after medicine administration,which was found 14 endogenous substances changed significantly,of which the content of phenylalanine,glutamic acid and tryptophan decreased,and the content of uric acid,oleic acid and ?-hydroxybutyric acid increased.HLF and RHV can reverse the abnormal changes mentioned above,and they might affect fatty acid metabolism and amino acid metabolism. |
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