Studying The Hypothyroidism And Medicine Of Yougui Pill Targets With Metabolism

ObjectiveClinical research:Through over the metabolomics testing of hypothyroidism patients and healthy volunteers’serum.Analysis endogenous metabolites differences within hypothyroidism patients, to investigate the biological nature of hypothyroidism, analysis metabolic pathways and metabolites differences may be involved.Animal experimental study:From the perspective of metabonomics compared to normal thyroid function and the decline of SD rat serum, look for related biomarkers, the analysis of features of hypothyroidism disease metabolites, research different dose right belongs to the pill on experimental Jiajian rats, the possible mechanism for treatment of traditional Chinese medicine or targets, understand the concentration-response relationship of Chinese traditional medicine, to find the best dosage regimens.MethodsUsing 1H-NMR metabolomics technology with pattern recognition method and SIMCA-P 12.0 statistical analysis.Clinical research:Collecting health and Jiajian group patients plasma sample, Analysising patients with hypothyroidism potential biomarker.Animal experimental study:The thyroid-functioned standard test sets out to analyse the traits and changes of serum metabolities from two experimental groups:the normal group and the underactive thyroid group. The methods used in this test are as follows, The test sets up a model for the experimental underactive thyroid mice, through the use of gastric lavage with sulfur. Based on this model, the underactive thyroid group was given Yougui pill for two months, compared to the group given euthyrox, Analysis of the Characteristics and Change of different doses of medicine YouguiWan experimental hypothyroidism rats serum metabolites.ResultsClinical research:There are different metabolic characteristics between healthy group and hypothyroidism group, Compared with normal group, materials in the serum of patients with hypothyroidism in unsaturated fatty acids, citric acid cycle metabolites (α-ketoglutarate and pyruvate), choline, citrulline, 3-hydroxybutyricacid, decreased. Phenylalanine, tyrosine, alanine, glycoprotein increased. Animal experimental study:Thyroid function:After modeling the Hypothyroidism of mice:Compared with control group, the mice with medicine started to behave as the hypothyroidism and asthenic after this modeling. What’s more the FT4、FT3 of the mice with medicine were evidently decline(P<0.01) to the normal data, also the TSH were higher than the control group, all the evident show us the modeling of Hypothyroidism had succeeded.After giving the treatment, the diffidence of contrasting the FT3, the medicine group, the middle-dose of using Youguiwan and the normal group has no statistic meanings because of the P＞0.05. Compared with the control group, there are statistic meanings because P<0.01 had been gone back to its normal scope also the low-dose of using Youguiwan and the high-dose of using Youguiwan have statistic meanings because of the P＜0.01. However, giving treatment had no statistic meanings compared to the control group because P>0.05 and didn’ t go back to the normal scope. For the FT4, the P of the groups giving Chinese herbology were lower than the normal group and the diffidence between the groups giving Chinese herbology and the normal group has the statistic meanings. Compared with the control group, their diffidence has no statistic meanings and show that the groups giving Chinese herbology and the FT4 hadn’t been back to the normal scope, what’s more the group giving western medicine was obviously higher than the normal group with statistic meanings. This result shows that Euthyrox can raise the FT4 to the mice with Hypothyroidism. For the TSH, the diffidence between the group giving western medicine and the normal group has no statistic meanings, but the diffidence between the group giving western medicine and the control group do have statistic meanings. It shows that the TSH of the group giving western medicine had been back to the normal scope. There have the statistic meanings when the groups giving Chinede herbology compared with the normal group but has no statistic meanings when compared with the control group, and show that the TSH of groups giving Chinese herbology hadn’t back to normal yet.Metabolomics aspects:1. After the building:compared with normal group, we found that after the building of SD rat serum metabolites vary:compared with normal control group, in the blood of the given model group rats serum creatinine, lactic acid, LDL and VLDL, N-acetyl glycoprotein content increases, unsaturated fatty acid, the Krebs cycle metabolites (citric acid, alpha glutaric acid and succinic acid), choline phosphate, citrulline,3-hydroxy butyric acid,0-acetyl glycoprotein content is lower.2. After giving medications:after building compared with before treatment, right to bolus dose group, high dose group, low dose group of western medicine group in serum the Krebs cycle product (citric acid, alpha ketone glutaric acid, succinic acid), citrulline content increased, cut down the content of lactic acid and right to bolus dose group, high dose group, western medicine group differences statistically significant, and right to pill low dose group compared with before treatment, there was no statistically significant difference; Western medicine and traditional Chinese medicine treatment group rats serum LDL and VLDL reduced from the previous, but statistically significant differences in western medicine group, the rest of the Chinese medicine treatment group there was no statistically significant difference; Unsaturated fatty acid, phosphoric acid, choline,3-hydroxy butyric acid content in serum of rats in the treatment group were compared with the previous, but only statistically significant differences in western medicine group, the rest of the Chinese medicine treatment group there was no statistically significant difference; Creatinine levels in each treatment group cuhk rat serum were reduced from the previous, difference have statistical significance; N-acetyl glycoprotein in the western medicine group rats serum content, to reduce the previous difference was statistically significant, in traditional Chinese medicine treatment group rats serum content is no obvious difference compared with the previous, no statistical significance; 0-acetyl glycoprotein in each treatment group cuhk rat serum levels were elevated earlier, difference has statistically significant.ConclusionClinical research:Patients with hypothyroidism exists in energy metabolism, lipid metabolism, amino acid metabolism, metabolism of phenylalanine, alanine glucose metabolism abnormalities. By metabolomics testing, There are differences between patients with hypothyroidism metabolites:choline, unsaturated fatty acid,3-hydroxybutyric acid, pyruvic acid, [alpha]-ketoglutarate, pyruvic acid, phenylalanine, tyrosine, glycoproteins, citrulline acid. These compounds may be the identification of objective indicators of hypothyroidism, providing a reference for early diagnosis of hypothyroidism.Animal experimental study:1. The tester had behaviour change of Deficiency hypothyroidism after taking those modeling pills. The clinical index of thyroid function, FT3 and FT4, had decreased, but the level of TSH had increased. In conclusion, the model was very successful in terms of animal symptom, mortality and the thyroid hormone level of serum.2. The Yougui pill had therapeutical effect to the underactive thyroid group. It could improve the symptoms of underctive thyroid, stimulate the body function in different level. A moderate amount of Yougui pill have effect to the level of thyroid hormone, and it can improve thyroid function.3. By nuclear magnetic resonance to detect hypothyroidism model rats differ from normal rat plasma metabolic profile group, lactic acid, LDL/VLDL, N-acetyl glycoproteins, elevated levels of citrulline, unsaturated fatty acids, citric acid cycle metabolites (citric acid, a-ketoglutarate and succinate), phosphorylcholine,3-hydroxybutyric acid,O-acetyl glycoproteins hypothyroidism may be potential biomarkers; YouguiWan large model can be adjusted hypothyroidism rat energy metabolism, certain lipid metabolism, protein metabolism of glucose.