Study On The Intervention Mechanism Of Yitangkang, A Traditional Chinese Medicine Compound, On Brown Fat In T2DM Rats Based On Metabolomics Technolog

Purpose:In this study,the effect of Yitangkang,a traditional Chinese medicine compound,on reducing blood sugar and treating type 2 diabetes mellitus was evaluated by comprehensive analysis of body weight,drinking water volume,fasting blood glucose value,inflammatory factors,etc.of type 2 diabetes rats;Through non targeted metabonomics analysis of brown adipose tissue,the mechanism of Yitangkang,a traditional Chinese medicine compound,in treating type 2 diabetes was explored,providing a new target for Yitangkang in treating T2 DM.Materials and methods:60 SPF Wistar male rats were selected,10 rats were randomly selected into the blank control group,fed with maintenance feed,and the remaining 50 rats were fed with high-fat feed,and STZ was injected intraperitoneally at a dose of 30 mg/kg to establish the model of type 2diabetes rats.Randomly divide the successfully modeled rats into 5 groups and provide different intervention measures.Normal control group and model control group rats were given 0.9% physiological saline 10 m L/kg/d by gavage,Yitangkang low,medium,and high-dose group rats were given traditional Chinese medicine compound Yitangkang low,medium,and high-dose 10 m L/kg/d by gavage,and Western medicine group rats were given pioglitazone hydrochloride 10 m L/kg/d by gavage,once a day,for 8 consecutive weeks.The fasting blood glucose,body weight,and water intake of rats were measured before and at the2 nd,4th,6th,and 8th weekends after modeling,and samples were taken at the 8th weekend.Enzyme linked immunosorbent assay(ELISA)was used to detect the levels of inflammatory factors IL-6 and UCP-1 in serum.Colorimetric method was used to determine the content of TG,TC,LDL-C,HDL-C,AST,and ALT in serum.The samples were separated using the SHIMADZU-LC30 ultra high performance liquid chromatography system(UHPLC)using LC-MS technology.The samples were separated by UPLC and analyzed using a QE Plus mass spectrometer(Thermo Scientific)for mass spectrometry.The original data was transformed using Sieve software(version 1.1.5,Thermo Fisher Scientific Inc.,USA),and pre processed with data such as desiccation and retention time correction.Then use Simca-P(version 14 1.Umetrics AB,Umea,Sweden)software for multivariate data statistical analysis.Analyze the changes in differential metabolites and metabolic pathways between each group.result:1.This experiment established a T2 DM rat model by inducing a high-fat diet in the early stage and injecting STZ intraperitoneally.The changes in the general condition of rats after modeling,as well as the changes in body weight,water intake,and blood sugar,all met the evaluation criteria for T2 DM rats compared to the blank group rats,indicating the successful establishment of the T2 DM animal model using this method.2.Among the 5 groups except for the blank group after intervention,the high-dose group of Yitangkang and the pioglitazone hydrochloride group had the best water intake control,which was superior to the medium and low dose groups of Yitangkang;In terms of weight control,the high-dose group of Yitangkang showed the most obvious trend of weight loss,which was better than the medium and low-dose groups of Yitangkang,while the pioglitazone hydrochloride group had a slightly worse trend;The fasting blood glucose of all four groups of rats improved,and the pioglitazone hydrochloride group had the best effect.3.The Yitangkang group can significantly upregulate the expression of UCP-1 and regulate energy metabolism in mice,but there is no significant statistical difference in the expression of IL-6.4.The monitoring results of rat blood lipid levels showed that compared with the normal control group,the model control group showed abnormalities in all blood lipid indicators,manifested as an increase in TC,TG,LDL-C,and a decrease in HDL-C.After intervention in the experimental group,the levels of TC,TG,LDL-C in each group of rats significantly decreased,while the levels of HDL-C significantly increased;Among them,Yitangkang high-dose group has the best effect on reducing TC,TG and LDL-C levels in type 2 diabetes rats,and the control group has the best effect on increasing HDL-C levels.5.Differential metabolic analysis: A total of 259 differential metabolites(VIP>1 and p<0.05)were detected as potential biomarkers for T2 DM in the model group and blank group.Compared with the model group,the Yitangkang group showed 257 different metabolites(VIP>1 and p<0.05)as potential biomarkers for the treatment of T2 DM.6.Differential metabolic pathway analysis: In the comparison test results between the blank group and the model group,a total of 29 differential metabolic pathways were analyzed,of which 16 pathways were upregulated and 13 pathways were downregulated.In the comparison test between the model group and the Yitangkang group,a total of 30 differential metabolic pathways were found,of which 14 pathways were upregulated and 16 pathways were downregulated.Conclusion:1.The traditional Chinese medicine compound Yitangkang can improve the general condition,body weight,blood sugar,and other indicators of T2 DM rats.2.The traditional Chinese medicine compound Yitangkang can improve the disorder of glucose and lipid metabolism in T2 DM rats.3.The traditional Chinese medicine compound Yitangkang can regulate the expression of IL-6and UCP-1 in T2 DM rats.4.Yitangkang,a traditional Chinese medicine compound,may regulate the concentration of2-oxoglutaric acid The metabolic levels of C17 sphingosine,L-alanine and threonine regulate lipid metabolism,amino acid metabolism,glucagon signal pathway and other metabolic pathways to improve metabolic abnormalities in rats.