针刺联合达英-35治疗多囊卵巢综合征痰湿证的作用靶点研究

Study on the therapeutic targets of acupuncture combined with Diane-35 in the intervention of phlegm-dampness syndrome of polycystic ovary syndrome

目的基于核磁共振氢谱(1H-NMR)检测技术,观察针刺联合达英-35治疗多囊卵巢综合征(PCOS)痰湿证对血清小分子代谢物代谢通路的影响,探讨其作用靶点。方法选择2018年5—11月于山东中医药大学附属医院中西医结合生殖与遗传中心门诊就诊的PCOS痰湿证患者40例,随机分成2组,每组20例。西药组于月经周期的第5天开始口服达英-35,连服21 d,治疗3个月经周期;针药联合组于口服达英-35同时给予针刺治疗,每周5次,周末和经期休息,治疗3个月经周期。记录2组治疗前后体质量指数(BMI);采用化学发光法检测2组治疗前后血清基础内分泌激素[促卵泡素(FSH)、促黄体素(LH)、雌二醇(E2)、睾酮(T)、空腹胰岛素(FINS)]水平,计算胰岛素抵抗指数(HOMA-IR);应用1H-NMR检测技术处理2组治疗后血清样本,筛选出血清中的代谢物及其参与的代谢通路。结果2组患者治疗前后FSH、E2水平组间及组内比较差异均无统计学意义(P均>0.05);2组患者治疗后BMI、LH、T、HOMA-IR均明显低于治疗前(P均<0.05),且针药联合组BMI、LH、T、HOMA-IR均明显低于西药组(P均<0.05)。针药联合组患者血清中的异亮氨酸、苯丙氨酸、酪氨酸、缬氨酸、谷氨酸等氨基酸,3-羟基丁酸酯、甘油等脂类,α-葡萄糖、β-葡萄糖等糖类物质均明显多于西药组(P均<0.05);西药组中二甲胺明显增多(P均<0.05)。2组存在一系列的糖代谢、脂代谢和氨基酸代谢通路差异,与西药组相比,针药联合组氨酰基-tRNA生物合成的富集程度更显著。结论针刺干预可明显调节PCOS痰湿证患者内分泌紊乱,其可能通过影响氨酰基-tRNA生物合成,以修复并调节线粒体aaRS活性为作用靶点,促进体内氨基酸代谢及糖脂代谢,起到治疗PCOS痰湿证的作用。

Objective It is to observe the effect of acupuncture combined with Diane-35 on the metabolic pathways of serum small molecule metabolites in the treatment of polycystic ovary syndrome(PCOS)of syndrome of phlegm-dampness based on nuclear magnetic resonance spectroscopy(1H-NMR)detection technique,and to explore its therapeutic targets.Methods Forty patients with PCOS of phlegm-dampness syndrome treated at the outpatient clinic of the Reproductive and Genetic Center of Integrated Traditional Chinese and Western Medicine,Shandong University of Traditional Chinese Medicine were selected,and randomly divided into 2 groups,with 20 cases in each group.The western medicine group started to take Diane-35 orally on the 5th day of the menstrual cycle for 21 days for 3 menstrual cycles;the acupuncture and drug combination group was given acupuncture treatment based on Diane-35 at the same time,5 times a week,rest on weekends and menstrual periods,treated for 3 menstrual cycles.The body mass index(BMI)of the two groups before and after treatment was recorded;the levels of serum basic endocrine hormones[follicle stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),testosterone(T),fasting insulin(FINS)]were detected by chemiluminescence,the insulin resistance index(HOMA-IR)was calculated;1H-NMR detection technology was used to exam the serum samples of the two groups after treatment,and the metabolites in the serum and the metabolic pathways involved were screened out.Results There was no significant difference in the levels of FSH and E2 between and within the two groups before and after treatment(P>0.05);BMI,LH,T,and HOMA-IR after treatment were significantly lower than those before treatment in the two groups(P all<0.05),and the BMI,LH,T,HOMA-IR of the combined acupuncture and medicine group were significantly lower than those of the western medicine group(all P<0.05).The serum amino acids such as isoleucine,phenylalanine,tyrosine,valine,glutamic acid,lipids such as 3-hydroxybutyrate,glycerol,carbohydrates such asα-glucose,β-Glucose in the combined acupuncture and medicine group were significantly higher than those in the western medicine group(all P<0.05);dimethylamine was significantly increased in the western medicine group(all P<0.05).There were a series of differences in glucose metabolism,lipid metabolism and amino acid metabolism pathways between the two groups.Compared with the western medicine group,the degree of enrichment of histidyl-tRNA biosynthesis was more significant in the combined acupuncture and medicine group.Conclusion Acupuncture intervention can significantly regulate endocrine disorders in patients with PCOS of phlegm-damp syndrome.It may affect aminoacyl-tRNA biosynthesis,repair and regulate mitochondrial aaRS activity as a target,promote amino acid metabolism and glucose and lipid metabolism in the body,thus to play a role in the treatment of PCOS of phlegm-dampness syndrome.