针刺对功能性便秘患者粪便代谢组学和血清炎症因子的影响

Effects of acupuncture on fecal metabolomics and serum inflammatory factors in patients with functional constipation

目的:探讨针刺对功能性便秘(FC)患者粪便代谢谱和血清炎症因子的影响。方法:纳入59例FC患者,随机分为针刺组(29例)和假针刺组(30例)。观察两组治疗前后周平均完全自主排便次数(CSBMs)≥3次的患者比例,周平均自主排便次数(SBMs)、Bristol粪便性状、排便困难程度及便秘患者生存质量自评(PAC-QOL)量表评分。采用液相色谱质谱联用(LC-MS/MS)检测、分析粪便代谢谱,描述代谢特征,筛选差异代谢物并基于KEGG富集代谢通路。Elisa检测白细胞介素(IL)-8和IL-10蛋白水平。最后进行代谢物与临床疗效指标、炎症因子的Spearman相关性分析。结果:与假针刺组比较,针刺组治疗后周平均CSBMs≥3次的比例更高(P<0.01),周平均SBMs、Bristol粪便性状评分和PAC-QOL较基线的改善程度更显著(P<0.05)。针刺治疗前后鉴定出22种特异性差异代谢物,主要富集于组氨酸、β-丙氨酸、生物素代谢等11条代谢通路。假针刺组仅鉴定出7种差异代谢物,未能形成有效富集。与治疗前比较,针刺组治疗后IL-8表达显著降低(P<0.01),而IL-10表达显著增加(P<0.01)。组氨酸、鹅去氧胆酸等15个针刺特异性代谢物与CSBMs、粪便性状评分的改善显著相关。同时,IL-10与组氨酸、前列环素呈显著正相关。结论:针刺可能通过调节FC患者粪便组氨酸、鹅去氧胆酸、前列环素等代谢物以及氨基酸、生物素代谢通路,降低IL-8水平,增加IL-10的分泌,减轻肠道低度炎症,恢复肠道动力。

Objective:To explore the effects of acupuncture on fecal metabolome and serum inflammatory factors in patients with functional constipation(FC).Methods:Fifty-nine FC patients were enrolled and randomly divided into acupuncture group(29 cases)and sham acupuncture group(30 cases).The proportion of patients with weekly average complete spontaneous bowel movements(CSBMs)≥3 times,weekly average spontaneous bowel movements(SBMs),Bristol stool characteristics,defecation difficulty degree and patient assessment of constipation quality of life(PAC-QOL)scale score were observed before and after treatment in both groups.Liquid chromatography-mass spectrometry(LC-MS/MS)was used to detect and analyze fecal metabolome,describe metabolic characteristics,screen differential metabolites and enrich metabolic pathways based on KEGG.Elisa was used to detect IL-8 and IL-10 protein levels.Finally,Spearman correlation analysis was performed between metabolites and clinical efficacy indicators,inflammatory factors.Results:Compared with the sham acupuncture group,the proportion of patients with weekly average CSBMs≥3 times was higher(P<0.01),and the improvement of weekly average SBMs,Bristol stool characteristics score and PAC-QOL was more significant(P<0.05)in the acupuncture group after treatment.Twenty-two specific differential metabolites were identified before and after acupuncture treatment,mainly enriched in 11 metabolic pathways such as histidine,beta-alanine,biotin metabolism.Only 7 differential metabolites were identified in the sham acupuncture group,and no effective enrichment was formed.Compared with before treatment,IL-8 expression was significantly decreased(P<0.01),while IL-10 expression was significantly increased(P<0.01)after acupuncture treatment.Fifteen acupuncture-specific metabolites,such as histidine,chenodeoxycholic acid,etc.,were significantly correlated with the improvement of CSBMs and stool characteristics score.At the same time,IL-10 was significantly positively correlated with histidine and prostaglandin.Conclusion:Acupuncture may regulate the fecal metabolites such as histidine,chenodeoxycholic acid,prostaglandin and the metabolic pathways such as amino acid,biotin metabolism in FC patients,reduce IL-8 level,increase IL-10 secretion,alleviate intestinal low-grade inflammation,and restore intestinal motility.