基于血清代谢组学研究左归丸与右归丸辨证治疗卵巢储备功能减退

Zuogui Pills and Yougui Pills in differential treatment of diminished ovarian reserve based on metabolomics

基于代谢组学系统分析左归丸与右归丸辨证治疗卵巢储备功能减退(DOR)的代谢物质基础,为中医辨证论治DOR提供科学依据。医院门诊收集DOR肾阴虚患者给予左归丸治疗12周,DOR肾阳虚患者给予右归丸治疗12周,基于非靶向代谢组学研究技术,筛选左归丸治疗DOR肾阴虚和右归丸治疗DOR肾阳虚的潜在生物标志物,并对其进行代谢通路分析。分别记录和统计患者治疗后的妊娠率及血清激素基础水平[基础卵泡刺激素(bFSH)、基础黄体生成素(bLH)、基础雌二醇(bE_(2))、抗缪勒管激素(AMH)]、中医证型评分、Kupperman评分的改变。结果显示,共收集DOR肾阴虚患者23例,肾阳虚患者25例。左归丸回调DOR肾阴虚患者的左旋肉碱、乙酰辅酶A、辅酶A、辅酶Q_(10)(CoQ10)等26种差异代谢物,映射到12条代谢通路;右归丸回调DOR肾阳虚患者的己二酰辅酶A、L-赖氨酸、赖氨酸精氨酸、α-生育酚等22种差异代谢物,映射到11条代谢通路。DOR肾阴虚和肾阳虚患者治疗后bFSH、bLH均明显低于治疗前,差异有统计学意义(P<0.05);虽然bE_(2)、AMH差异没有统计学意义,但有改善趋势;中医证型评分和Kupperman评分均明显低于治疗前,差异有统计学意义(P<0.05)。

Based on the metabolomics,this paper systematically analyzed the metabolic substance basis of Zuogui Pills and Yougui Pills in syndrome differentiation and treatment of diminished ovarian reserve(DOR),so as to provide a scientific basis for the traditional Chinese medicine(TCM) syndrome differentiation and treatment of DOR.Patients with DOR of kidney-Yin deficiency syndrome were collected from outpatient department of hospitals and treated with Zuogui Pills for 12 weeks.And kidney-Yang deficiency syndrome were treated with Yougui Pills for 12 weeks.Based on the non-targeted metabolomic research techniques,the potential biomarkers of Zuogui Pills and Yougui Pills in the treatment of DOR with kidney-Yin deficiency and kidney-Yang deficiency,respectively,were screened out,and metabolic pathways of biomarkers were analyzed.The pregnancy rate,basic serum hormone levels [basal follicle-stimulating hormone(bFSH),basal-luteinizing hormone(bLH),basal-estradiol(bE_2),and anti-Müllerian hormone(AMH)],TCM syndrome type score,and Kupperman score were recorded and statistically analyzed after treatment.The results showed that 23 patients with DOR of kidney-Yin deficiency syndrome and 25 patients of kidney-Yang deficiency syndrome were collected.Twenty-six differential metabolites,including L-carnitine,acetyl-CoA,coenzyme A,and coenzyme Q_(10)(CoQ10),were mapped to 12 metabolic pathways in patients with kidney-Yin deficiency treated with Zuogui Pills.Twenty-two differential metabolites,such as adipoyl-CoA,L-lysine,lysine arginine,and α-tocopherol,were mapped to 11 metabolic pathways in patients with kidney-Yang deficiency.After treatment,bFSH and bLH of patients with DOR were significantly lower than those before treatment(P<0.05).Although the comparison of bE_(2) and AMH had no significant differences,there was a improvement trend.The TCM syndrome type score and Kupperman score of patients with DOR after TCM treatment were significantly lower than those before treatment(P<0.05).