小金丸治疗脾肾阳虚型甲状腺功能减退期桥本甲状腺炎的氨基酸代谢组学研究

Amino acid metabolism research of Xiaojin Pills in the treatment of hypothyroidism phase of Hashimoto's thyroiditis in spleen-kidney yang deficiency

目的:探究小金丸治疗甲状腺功能减退期桥本甲状腺炎的氨基酸代谢相关作用机制。方法:将47例甲状腺功能减退期桥本甲状腺炎患者随机分为对照组(22例)、小金丸组(25例),利用超高效液相色谱-四极杆静电场轨道阱高分辨质谱法技术分别检测两组患者治疗前后血清14种氨基酸代谢物水平。再用偏最小二乘判别分析(PLS-DA)、正交偏最小二乘法-判别分析(OPLS-DA)分析比较组间代谢物差异。筛选差异性代谢物,使用MetaboAnalyst网站分析相关代谢通路。结果:与治疗前比较,小金丸组患者治疗后血清中天冬酰胺水平显著升高(P<0.05),丝氨酸、蛋氨酸水平显著降低(P<0.05);与对照组比较,小金丸组治疗后丙氨酸水平显著升高(P<0.05),色氨酸、苯丙氨酸、蛋氨酸水平显著降低(P<0.01)。相关性分析显示患者血清色氨酸水平与促甲状腺激素(TSH)呈显著负相关(P<0.01)、与游离三碘甲状腺原氨酸(FT3)呈显著正相关(P<0.01);丝氨酸与游离甲状腺素(FT4)显著负相关(P<0.01)、与甲状腺过氧化物酶抗体(TPOAb)显著正相关(P<0.01)。结论:小金丸通过参与体内多种氨基酸代谢途径,干预细胞免疫反应及炎症反应,改善机体免疫系统功能,降低甲状腺自身抗体水平。

Objective:To explore the mechanism of amino acid metabolism in the treatment of hypothyroidism phase of Hashimoto's thyroiditis.Methods:Forty-seven patients with hypothyroidism phase of Hashimoto's thyroiditis were randomly divided into control group(22 cases)and Xiaojin Pills group(25 cases),and 14 amino acid metabolites were measured by ultrahigh performance liquid chromatography-quadrupole electrostatic field orbitwell high resolution mass spectrometry.Metabolite differences were then compared by partial least squares discriminant analysis(PLS-DA)and orthogonal partial least squaresdiscriminant analysis(OPLS-DA).Differential metabolites were screened and associated metabolic pathways were analyzed using the MetaboAnalyst website.Results:After treatment of Xiaojin Pills,the serum levels of asparagine increased(P<0.05)and serine and methionine decreased(P<0.05)when compared before the treatment.Compared with the control group,the levels of alanine increased(P<0.05),tryptophan and phenylalanine and methionine decreased(P<0.01)in the Xiaojin Pills group.Correlation analysis showed a significant negative correlation between patient serum tryptophan levels and TSH(P<0.01),and a significant positive correlation with FT3(P<0.01);serine was significantly negatively associated with FT4(P<0.01)and significantly positively associated with TPOAb(P<0.01).Conclusion:By participating in a variety of amino acid metabolic pathways in the body,Xiaojin Pills interferes in the cellular immune response and inflammatory response,improves the function of the body's immune system,and reduces the level of thyroid autoantibodies.