基于代谢组学探讨金藤清痹颗粒治疗类风湿关节炎的作用机制

Action Mechanism of Jinteng Qingbi Granule in Treatment of RA Based on Metabonomics

目的:基于代谢组学的方法探讨金藤清痹颗粒治疗类风湿关节炎(RA)的作用机制。方法:将SPF级健康SD雄性大鼠30只随机分为对照组(Control组)、模型组(Model组)、双氯芬酸钠阳性药组(SLFSN组)、金藤清痹颗粒高剂量组(JTQB-H组)和金藤清痹颗粒低剂量组(JTQB-L组)。Control组和Model组大鼠灌胃给予生理盐水,其余各组灌胃给予相应药物,给药28 d。除对照组外,其余各组采用胶原诱导RA大鼠模型。HE染色观察大鼠踝关节病理变化,酶标仪检测大鼠血清相关炎症指标,UPLC-Q-TOF/MS筛选金藤清痹颗粒干预RA大鼠后的差异代谢物。结果:与Control组比较,Model组大鼠踝关节肿胀明显,滑膜细胞增生并伴随大量炎性细胞浸润,显著升高血清TNF-α、IL-1β、RF水平(P<0.01);与Model组比较,金藤清痹颗粒各剂量组可明显缓解RA模型大鼠关节肿胀度,改善踝关节炎性浸润,JTQB-H组可显著降低RA大鼠血清TNF-α、IL-1β水平(P<0.05);代谢组学共筛选出包括DL-丝氨酸、L-赖氨酸、高脯氨酸在内的12个差异代谢物;KEGG通路分析显示,金藤清痹颗粒治疗RA主要通过调控甘氨酸,丝氨酸和苏氨酸代谢、亚油酸代谢、苯丙氨酸代谢等通路来发挥疗效。结论:金藤清痹颗粒治疗RA的作用机制可能与调控多条氨基酸代谢通路有关。

Objective:To investigate the mechanism of Jinteng Qingbi Granule in treatment of rheumatoid arthritis(RA)based on metabolomics.Methods:30 SD rats were randomly divided into the control group,the model group,the Diclofenac sodium group,the Jinteng Qingbi(JTQB)groups of high-dose and low-dose.RA model was induced by using collagen.After 28 days of intervention,pathological changes in the ankle joint area of rats were observed by HE staining,serum-related inflammatory indexes were detected by Elisa method,and differential metabolites of JTQB were screened out by UPLC-Q-TOF/MS.Results:Compared with those in the control group,the ankle swelling,synoviocyte proliferation and inflammatory cell infiltration could be seen,the serum levels of TNF-α,IL-1β and RF were significantly increased in the model group(P<0.01).Compared with those in the model group,the joint swelling and inflammatory infiltration were significantly alleviated,and the serum levels of TNF-α and IL-1β were significantly reduced in the JTQB-H group(P<0.05).Metabolomics screened 12 different metabolites including DL-serine,L-lysine and hyperproline.KEGG analysis showed that the treatment of RA with JTQB Granule was mainly through the regulation of metabolisms of glycine,serine,threonine,linoleic acid and phenylalanine.Conclusion:The action mechanism of Granule JTQB may be related to the regulation of multiple amino acid metabolic pathways in treatment of RA.