The Metabonomic And Pharmacodynamic Study On Buzhong Yiqi Decoction In Treating The Spleen Qi Deficiency

ObjectiveTo study the metabolic profiling of CSG (chronic superficial gastritis) patients with SQD(spleen-qi deficiency) and treatment after Buzhong Yiqi decoction(BZYQD) perspective from metabonomics, and to search the biomarkers related to CSG and BZYQD combined with clinical observation. Further integration of metabolomics studies, we focus on the regulation of glucose metabolism, and discuss the related substances with digestion and metabolism, in order to explain the scientific connotation of BZYQD from the metabolic level, to provide reasonable scientific basis for the rational application of BZYQD, and to investigate the essence of TCM symptoms from the systems biological level and to provide an objective basis for clinical diagnosis and treatment of CSG disease.Methods①Metabolomics Study on BZYQD in treatment of CSG Patients with SQDUrines from individuals with SQD,4week and8week after BZYQD treatment, and HV(healthy volunteers) were collected respectively. lH-NMR based metabonomic analysis was performed on above samples, PCA(principal component analysis) and PLS-DA(partial least squares discriminant analysis) were used to find the metabolic fingerprinting differences among CSG patients with SQD and their after administration, and VIP(variable importance projection) and single variable statistical analysis (t-test) were taken to screen the related biomarks.②Pharmacological study of BZYQD on related links of glucose metabolism of Rats with SQD Rat model of SQD was established by an combined method of administration of the liquor and vinegar, exhaustive strength swimming, and starvation. The model rats were randomly divided into the model group, the BZYQT group, the group of BZYQT with double Astraglus (double group) and the group of BZYQT with half Astraglus(half group), respectively dose the groups. In the experiments the physical sign was noted and the activity of H+/K+ATPase in gastric mucosa, GK in hepatic tissue, AMS、LDH、SDH and IDH in serum was detected. AchievementsThe study showed that:①Symptoms scores and frequency of both the main symptoms as body tired fatigue, abnormal defecation and the secondary symptoms of sallow complexion, laziness to speak with fatigued spirit, tastelessness and no thirst from CSG patients with SQD were highest. PCA analysis showed the two groups of HV and CSG patients with SQD had a tendency to separate, further PLS-DA analysis showed two groups of samples in the PLS-DA scores plot were in a clear separation, which indicated that the metabolites between individuals with SQD and HV were different. Nine potential biomarkers were selected from urine between SQD and HV, which mainly reflected on the SQD urine taurine, glucose rising, and glutamic acid, methionine, glycine, creatinine, and α-Oxoglutarate decreasing.②Clinical symptoms of the4week(12.9±6.3) and8week(8.9±4.2) improved significantly when compared with prior treatment(23.6±8.0)(P<0.05). PCA analysis showed the four groups among CSG patients with SQD, the twice treatments after BZYQD, and HV had a certain tendency to separate, and the urinary metabolic profiling after administration were close to that of HV, but there were little difference between the4and8week. PLS-DA analysis showed that metabolites before and after BZYQD treatment were different obviously, and ten potential biomarkers were selected from urine related with BZYQD, which mainly reflected on the urine methylsuccinic acid, a-Oxoglutarate,β-hydroxybutyric acid, valine, tyrosine, creatinine, phenylaceturic acid and hippuric acid rising, while glucose, uridine decreasing after administration.③The SQD rat model manifested the decreasing in serum AMS and LDH level, and the increasing in H+/K+ATPase of gastric mucosa, GK activity of hepatic tissue, while no significant changes in serum SDH and IDH. After drug treatment, in rats of the BZYQT group, serum AMS and LDH level increased markedly (P<0.05), H+/K+ATPase and GK decreased significantly(P<0.05); in the double group, the activity of AMS, H+/K+ATPase, LDH and GK improved but less than the BZYQT group; in the half group, the above four indexs changed little(P>0.05); simultaneously, the activity of SDH and IDH in serum had no statistic difference among groups(P>0.05).ConelusionsCSG with SQD presents the abnormal catabolism of amino acids, inhibition of tricarboxylic acid cycle(TCA), and accompanied with certain liver and kidney dysfunction. The mechanism of BZYQD improving the CSG patients with SQD of syndromes as body tired fatigue and laziness to speak with fatigued spirit may be related to its ability to enhance the energy metabolism, especially for the regulation of glucose metabolism. BZYQD can improve the low digestion and absorption of SQD rats, improve the anaerobic oxidative metabolism and regulate the glucose level of SQD rats, and reduce the gastrointestinal mucosa damage by controlling the amount of gastric acid secretion, in particular astragalus dosages30gram, but its effect to TCA remains further study.