基于代谢组学研究针刺腰痛点治疗泌尿系结石肾绞痛的作用机制

Mechanism of acupuncture at Yaotong dian for renal colic caused by urinary calculi based on metabonomics

目的观察针刺腰痛点治疗泌尿系结石急性肾绞痛的有效性,并基于代谢组学探讨其作用机制。方法本研究为探索性随机对照试验,将20例泌尿系结石肾绞痛患者随机分为试验组与对照组,每组各10例。试验组采用针刺双侧腰痛点,对照组采用非穴点浅刺治疗。观察比较2组患者针刺操作后10 min的疼痛缓解率;治疗前后采用色谱-质谱联用技术的非靶向代谢组学方法对2组血清进行检测。对检测出的代谢物根据P值、差异倍数变化以及计算变量投影重要度值进行差异筛选,利用Spearman相关系数,与临床指标相结合,进行差异代谢物的进一步筛选,基于KEGG数据库进行功能通路富集分析。结果针刺操作后10 min,试验组较对照组获得更高的疼痛缓解率80.0%(95%CI 38.4%~94.3%,P<0.01)。代谢组学:试验组治疗前后对比,筛选出差异代谢物199个;对照组治疗前后对比,筛选出差异代谢物54个;试验组对比对照组,筛选出差异代谢物325个。对试验组治疗前后代谢物变化与NRS疼痛评分Spearman等级相关分析发现,鸟苷等4个差异代谢物与NRS疼痛评分呈负相关,阿尔巴黄酮等9个差异代谢物与NRS疼痛评分呈正相关;试验组较对照组代谢物变化与NRS疼痛评分Spearman等级相关分析发现,3-醛基水杨酸等3个差异代谢物与NRS疼痛评分呈负相关,皮质醇等8个差异代谢物与NRS疼痛评分呈正相关。试验组对比对照组,富集到通路9条,其中与疼痛调节相关的通路为色氨酸代谢途径和不饱和脂肪酸的生物合成代谢途径。结论针刺腰痛点可快速缓解泌尿系结石肾绞痛,调节鸟苷、鸟嘌呤、皮质醇等代谢产物表达,影响色氨酸代谢途径与不饱和脂肪酸的生物合成代谢途径,可能是针刺治疗肾绞痛的潜在作用机制。

Objective To observe the effectiveness of acupuncture at the Yaotong dian(EX-UE7)in the treatment of acute renal colic caused by urinary tract stones and explore its mechanism of action from a metabolomics perspective.Methods This study was an exploratory prospective randomized controlled trial.20 patients with acute renal colic due to urolithiasis were randomly divided into an experimental group(10 cases)and a control group(10 cases).The experimental group received acupuncture at the bilateral Yaotongdian(EX-UE7).The control group was treated with nonpoint shallow puncture.The outcome was the response rate at 10 minutes after needle manipulation.The nontargeted metabolomics method of chromatography-mass spectrometry was used to detect the metabolites in each group of samples before and after treatment.The detected metabolites were differentiated according to P value,difference multiple change and the projected importance value of calculated variables,and the Spearman correlation coefficient was used to combine with clinical indicators for further screening of differential metabolites.Functional pathway enrichment analysis was done based on the KEGG database.Results The experimental group benefited from higher response rate of 80.0%at 10 minutes than the control group(95%CI,38.4%~94.3%,P<0.01).In terms of metabolomics,199 differential metabolites were screened before and after treatment in the experimental group;54 differential metabolites were screened before and after treatment in the control group.Compared with the experimental group,325 different metabolites were screened from the control group.Spearman level correlation analysis was performed on the changes in metabolites and NRS pain scores before and after treatment in the experimental group,the results showed that 4 different metabolites including guanosine were negatively correlated with NRS pain scores.9 different metabolites including Albaflavenone were positively correlated with the NRS pain scores.Spearman correlation analysis was conducted between the changes in metabolites in the control group and those in the experimental group and the NRS pain scores.The results showed that 3 different metabolites including 3-aldehyde salicylic acid were negatively correlated with the NRS pain scores.8 different metabolites including Cortisol were positively correlated with the NRS pain scores.Compared with the control group,the experimental group was enriched in 9 pathways,among which the pathways related to pain regulation were the tryptophan metabolism pathway and unsaturated fatty acid biosynthetic metabolism pathway.Conclusion Acupuncture at the bilateral Yaotongdian(EX-UE7)can be considered an effective therapy in relieving acute renal colic caused by urinary tract stones.Guanine,guanosine,cortisol different metabolites are associated with changes in pain,and tryptophan metabolic pathways and unsaturated fatty acid biosynthesis pathways also participates in the regulation of pain,which may be the potential mechanism of acupuncture in the treatment of renal colic.