Guo Yao-Guang, Sun Guang-Wei, Yang Ling, Li Cong, Yang Jiao
Department of Acupuncture and Moxibustion, Affiliated Hospital of Chengdu University of TCM, Chengdu 610072, China.
Department of Oncology, Sichuan Integrative Medicine Hospital, Chengdu 610000.
Zhen Ci Yan Jiu. 2021 Feb 25;46(2):145-51. doi: 10.13702/j.1000-0607.200181.
To analyze the endogenous metabolic biomarkers and pathways in serum involving acupuncture-induced improvement of symptoms of patients with rheumatoid arthritis (RA) by using metabolomics technique.
A total of 30 RA patients who were treated in the Department of Acupuncture and Moxibustion of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine (from January 2018 to October 2018) were selected in the present study. They were randomly and equally divided into acupuncture group and medication group. Acupuncture (lifting-thrusting reinforcing and uniform reducing-reinforcing methods) was applied to bilateral Fengchi (GB20), Yangchi (TE4), Quchi (LI11), Yingu (KI10), Taixi (KI3), Xuehai （SP10）, Guanyuan (CV4), Yanglingquan (GB34) and Ashi-points for 20 min every time, once daily for 3 months. Patients of the medication group were asked to take Tripterygium Wilfordii Polyglycoside tablets (a positive drug for RA, one tablet per time, 3 times a day) for 3 months. Other 10 healthy volunteers were selected as the normal control group. The tenderness scale (0-4 points) and swelling scale (0-3 points) and morning stiffness time were recorded, and serum rheumatoid factor (RF), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were detected for analyzing pharmacodynamic effects. Serum samples were captured for profiling and quantifying metabolite biomarkers by using GC-MS (gas chromatography-mass spectrometry) technique. The acquired metabolite profiles were processed (multivariable data analysis) by using ProteoWizard package, XCMS Online software and SIMCA 13.0 software, respectively, followed by screening differential metabolites according to variable importance projection (VIP) and by constructing metabolic pathways with MetaboAnalyst 4.0.
After acupuncture treatment, the tenderness score, swelling score, morning stiffness time, serum RF and CRP contents were significantly decreased in both acupuncture and medication groups in comparison with their own pretreatment (P<0.05). No significant differences were found between acupuncture and medication groups in the levels of tenderness score, swelling score, morning stiffness time, serum RF and CRP contents (P>0.05). A total of 14 differential metabolites including citrate, creatine, 3-hydroxybutyrate arachidonic acid, arachidonic acid, valine, lactic acid and palmitic acid (up-regulated), and tryptophan, arginine, L-phenylalanine, glucose, glycine, glutamine, aspartic acid and (down-regulated) which mainly involve metabolic pathways of alanine, aspartic acid and glutamate; metabolism of phenylalanine, tyrosine and tryptophan; metabolism of glycine, serine and threonine; glyoxalic acid dicarboxylic acid metabolism; metabolism of starch and sucrose; and metabolism of phenylalanine and arachidonic acid, respectively.Citrate, creatine, arachidonic acid, valine and glucose was positively correlated with tenderness index, swelling index, morning stiff time, RF, CRF and ESR. Glycine, L-phenylalanine , glutamine was negatively correlated with efficacy indicators.
Acupuncture can relieve symptoms of patients with RA, which may be related to its effects in improving amino acid metabolism and glucose metabolism.
采用代谢组学技术分析血清中的内源性代谢生物标志物及通路，探讨针刺改善类风湿关节炎（RA）患者症状的机制。
选取成都中医药大学附属医院针灸科2018年1月至2018年10月收治的30例RA患者，随机分为针刺组和药物组，每组15例。针刺组采用提插补泻和平补平泻手法针刺双侧风池（GB20）、阳池（TE4）、曲池（LI11）、阴谷（KI10）、太溪（KI3）、血海（SP10）、关元（CV4）、阳陵泉（GB34）及阿是穴，每次留针20 min，每日1次，连续治疗3个月。药物组口服雷公藤多苷片（RA阳性对照药，每次1片，每日3次），连续服用3个月。另选取10名健康志愿者作为正常对照组。记录患者压痛程度（0～4分）、肿胀程度（0～3分）及晨僵时间，并检测血清类风湿因子（RF）、C反应蛋白（CRP）及红细胞沉降率（ESR），分析针刺和药物治疗的药效学作用。采用气相色谱-质谱联用（GC-MS）技术对血清样本进行代谢物生物标志物的定性和定量分析。分别使用ProteoWizard软件包、XCMS Online软件和SIMCA 13.0软件对获得的代谢物谱进行处理（多变量数据分析），然后根据变量重要性投影（VIP）筛选差异代谢物，并使用MetaboAnalyst 4.0构建代谢通路。
针刺组和药物组治疗后压痛评分、肿胀评分、晨僵时间、血清RF及CRP含量较治疗前均显著降低（P<0.05），针刺组与药物组治疗后上述指标比较，差异无统计学意义（P>0.05）。共筛选出14种差异代谢物，其中柠檬酸、肌酸、3-羟基丁酸、花生四烯酸、缬氨酸、乳酸和棕榈酸（上调），色氨酸、精氨酸、L-苯丙氨酸、葡萄糖、甘氨酸、谷氨酰胺、天冬氨酸（下调），主要涉及丙氨酸、天冬氨酸和谷氨酸代谢途径；苯丙氨酸、酪氨酸和色氨酸代谢；甘氨酸、丝氨酸和苏氨酸代谢；乙醛酸二羧酸代谢；淀粉和蔗糖代谢；苯丙氨酸和花生四烯酸代谢。柠檬酸、肌酸、花生四烯酸、缬氨酸和葡萄糖与压痛指数、肿胀指数、晨僵时间、RF、CRF和ESR呈正相关。甘氨酸、L-苯丙氨酸、谷氨酰胺与疗效指标呈负相关。
针刺可缓解RA患者症状，可能与其改善氨基酸代谢和糖代谢有关。
