RESUMO
Plasma metabolomics based on UHPLC-Q-TOF-MS/MS technique was developed for profiling the mechanism on attenuating hepatic fibrosis of Bupleuri Radix (BR) and Paeoniae Radix Alba (PRA) before and after vinegar-processing and compatibility, and to screen potential pharmacodynamic substances by spectrum-effect correlation method in this study. Firstly, SD rats with CCl4-induced hepatic fibrosis were used as an in vivo model. The blood and tissue samples were collected for the analyses of pharmacodynamic indexes and plasma metabolomics after six weeks’ administration of BR, vinegar-processed BR (VPBR), PRA, vinegar-processed PRA (VPPRA), BR-PRA herb-pair, and VPBR-VPPRA herb-pair. The experiment was approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (No.202103A002). The results of pharmacodynamics indicated that the levels of alanine aminotransferase (ALT, P < 0.01), aspartate aminotransferase (AST, P < 0.01), and hydroxyproline (HYP, P < 0.01) were decreased significantly, while the level of glutathione peroxidase (GSH-Px, P < 0.05) was increased obviously after administration of all treatment groups. Next, UHPLC-Q-TOF-MS/MS was performed to characterize the endogenous metabolites. A total of 20 differential endogenous metabolites related to the pathogenesis of hepatic fibrosis were identified in positive and negative ion modes, mainly involving five metabolic pathways of retinol metabolism, glycerol phospholipid metabolism, glyceride metabolism, fatty acid biosynthesis, and arachidonic acid metabolism. Meanwhile, a concept named correction rate was introduced to evaluate the back-regulation effects of all treatment groups on differential metabolites, and 10 differential metabolites were corrected by all treatment groups. The correction effects of the vinegar-processed herb groups were better than those of the crude ones, and the correction effects of the herb-pair groups were better than those of the single ones. Interestingly, the best correction effect was found in the VPBR-VPPRA herb-pair group, which further verified the efficacy improvement through vinegar-processing and compatibility. Partial least square method and VIP analysis combined with spectrum-effect correlation were applied for screening pharmacodynamic markers, and 38 ingredients with higher correlation with four classical pharmacodynamic indexes (ALT, AST, HYP, and GSH-Px) were identified as pharmacodynamic markers of the anti-hepatic fibrosis effects of BR and PRA before and after vinegar-processing and compatibility. The results of the investigation could not only lay a foundation for clarifying the pharmacodynamic materials and mechanism of vinegar-processing and compatibility of BR and PRA in the treatment of hepatic fibrosis as well as provide a theoretical basis for demonstrating the scientific connotation of processing and compatibility, but also provide a reference for further drug design and development of BR and PRA in clinic.
RESUMO
<p><b>OBJECTIVE</b>To investigate the effects of electro-acupuncture (EA) combined general anesthesia on myocardial injury of high blood sugar patients with coronary heart disease (CHD) in the perioperative phase.</p><p><b>METHODS</b>Recruited were 40 senile patients with glycosylated hemoglobin (HbA1c) more than 6.5%. They were more than 60 years old. They received post-traumatic fracture reduction surgery of four limbs. They were randomly assigned to two groups, Group N (treated by general intravenous anesthesia) and Group D (treated by EA combined with general intravenous anesthesia), 20 in each group. All patients were maintained anesthesia by propofol, fentanyl, and vecuronium. Prior to the induction of anesthesia, patients in Group D received induction of EA at Neiguan (PC6) and Baihui (DU20) for 20 min, which lasted to the end of the surgery. At before intubation (T0), immediately after intubation (T1), 5 min (T2), immediately after extubation (T3), 5 min (T4), 60 min (T5), 180 min (T6), the fast blood glucose (FBG), plasma vasoactive substance TXB2 and 6-K-prostacycline (6-K-PGF1alpha) were detected in the two groups. The glucose coefficient of variation (GluCV) and the ratio of TXB2/6-K-PGF1alpha were calculated. The changes of ST-segment elevation (mV, sampling 1 min after each time point, and the mean calculated) was recorded.</p><p><b>RESULTS</b>There was no statistical difference in all the tested values between the two groups at T0 (P>0.05). The FBG, ST elevation, and the ratio of TXB2/6-K-PGF1alpha were significantly higher at each time point than at T0 in Group N (P<0.05), while there was no statistical difference in Group D (P>0.05). The ratio of TXB2/6-K-PGF1alpha and ST elevation were significantly higher in Group N than in Group D (P<0.01). The TXB2 and 6-K-PGF1alpha were significantly higher at each time point than at T0 in the two groups (P<0.05). The increment of TXB2 was obviously lower in Group D than in Group N (P<0.05), but the increment of 6-K-PGF1alpha was obviously higher in Group D than in Group N (P<0.05).</p><p><b>CONCLUSION</b>EA could reduce the perioperative stress response to the injury of coronary vascular endothelial cells, and improve myocardial ischemia and CHD patients' prognosis by regulating the central nervous system, the cardiovascular active substances, and anti-oxygen free radicals.</p>