Study On The Effect Of Xiaojin Pill On Subclinical Hypothyroidism Of Hashimoto’s Thyroiditis Based On Metabolomics

Objective:Based on the study of metabonomics,this paper studies the changes of serum differential metabolites and related metabolic pathways of Xiaojin Pill in patients with subclinical hypothyroidism of Hashimoto’s thyroiditis before and after treatment,and explores the mechanism of Xiaojin Pill from the aspect of metabonomics,so as to provide an objective basis from the perspective of metabonomics for the treatment of Hashimoto’s thyroiditis with traditional Chinese medicine(TCM).Methods:1.107 patients were randomly divided into three groups: group A(n=32)was treated with Xiaojin Pill,group B(n=33)was treated with Euthyrox,and group C(n=42)was treated with Xiaojin Pill plus Euthyrox.The treatment lasted for 30 days,serum samples were collected before and after treatment to detect the relevant indicators.The serum samples before treatment were marked as group A0,group B0 and group C0,and the serum samples after treatment were marked as group A1,group B1 and group C1.2.The changes of serum thyroid stimulating hormone(TSH),thyroid peroxidase antibody(TPOAb)and thyroglobulin antibody(Tg Ab)were detected by electrochemiluminescence immunoassay.3.The differential metabolites before and after treatment were analyzed by UPLC-Q-Exactive Orbitrap MS and the maps were collected.4.The data were extracted and preprocessed by Compound Discoverer software,and then the processed data were analyzed by principal component analysis and orthogonal partial least square discriminant analysis by SIMCA(V14.1)software.The differential metabolites were screened according to the variable projection importance(VIP)and the P-value of Student’s t-test.The metabolic pathways involved in differential metabolites were analyzed by KEGG database,through enrichment and topological analysis to find the key metabolic pathways.Results:1.Xiaojin Pill or Euthyrox alone and their combination were effective in reducing the total score of TCM symptoms and improving the curative effect of TCM syndromes.After treatment,the total effective rates of TCM symptoms in Xiaojin Pill group and combination group were 96.88% and97.62%,respectively.The curative effect was better than that of Euthyrox group(P<0.01).2.Xiaojin Pill or Euthyrox alone and their combination have a certain clinical effect on reducing TSH,TPOAb and Tg Ab.The curative effect of Xiaojin Pill group in reducing TPOAb and Tg Ab is better than that of Euthyrox group(P<0.05).The combination of two drugs can reduce TSH,TPOAb and Tg Ab at the same time(P<0.05 or P<0.01).3.Compared with before treatment,there were 9 different metabolites in Xiaojin Pill group,including 7 metabolites such as creatine and proline up-regulated,N-isoamylglycine and uric acid down-regulated.Xiaojin Pill mainly improves human metabolism and treats diseases through tricarboxylic acid cycle,amino acid metabolism,phenylalanine metabolism,purine metabolism and lipid metabolism pathways.4.After treatment,there were 16 differential metabolites between Xiaojin Pill group and Euthyrox group,12 metabolites such as creatinine,nicotinamide and glutamine were up-regulated,and 4 metabolites such as piperidine acid and N-leucine were down-regulated.The main metabolic pathways involved in serum differential metabolites are tricarboxylic acid cycle,amino acid metabolism,phenylalanine metabolism,lipid metabolism and purine metabolism.5.After treatment,there were 12 differential metabolites between Xiaojin Pill plus Euthyrox group and Xiaojin Pill group,8 metabolites such as hippuric acid,proline and L-tyrosine were up-regulated,and 4 metabolites such as piperidine acid and N-leucine were down-regulated.The main metabolic pathways involved in serum differential metabolites are tricarboxylic acid cycle,amino acid metabolism,fatty acid metabolism,phenylalanine metabolism and purine metabolism.6.After treatment,there were 21 differential metabolites between Xiaojin Pill plus Euthyrox group and Euthyrox group,15 metabolites such as hippuric acid and L-tyrosine were up-regulated,and 6 metabolites such as piperidine acid and urine were down-regulated.The main metabolic pathways involved in serum differential metabolites are amino acid metabolism,tricarboxylic acid cycle,phenylalanine metabolism,tryptophan metabolism,lipid metabolism,fatty acid metabolism and purine metabolism.Conclusion: Xiaojin Pill can reduce the levels of TPOAb and Tg Ab in subclinical hypothyroidism patients with Hashimoto’s thyroiditis,reduce the total score of TCM symptoms and increase the clinical efficacy of TCM.Due to the limitation of research funds the mechanism of Xiaojin Pill in the treatment of HT was explored from the point of view of metabonomics.Research found metabonomic differential metabolism is characterized by the changes of tricarboxylic acid cycle,amino acid metabolism,phenylalanine metabolism and purine metabolism.This disease can be treated by enhancing energy metabolism and phenylalanine metabolism,improving immune response and reducing TSH release.From the perspective of clinical observation and metabonomics,this study explored the exact efficacy and mechanism of Xiaojin Pill,which provided an objective basis for the treatment of Hashimoto’s thyroiditis with TCM.