独活寄生汤治疗肝肾亏虚型膝骨关节炎患者临床疗效及关节液代谢组学变化

Clinical Efficacy of Duhuo Jisheng Tang in Treatment of Patients with Liver and Kidney Deficiency Type Knee Osteoarthritis and Changes in Joint Fluid Metabolism

目的:观察独活寄生汤治疗肝肾亏虚型膝骨关节炎(knee osteoarthritis,KOA)的临床疗效,并分析经独活寄生汤治疗前后关节液中小分子化合物的变化。方法:将73例天津中医药大学第一附属医院确诊的KOA患者随机分为观察组(42例)及对照组(31例),观察组给予独活寄生汤150 m L/次,2次/d,口服,对照组给予硫酸氨基葡萄糖胶囊0.5 g/次,3次/d,口服,两组患者均治疗1个月,以膝关节视觉模拟评分法(visual analogue scale score,VAS),西安大略麦马斯特大学骨关节炎指数评分(The Western Ontario and Mc Maste Universities,WOMAC),自制膝关节肿胀评分及综合疗效治疗反应评价作为临床疗效判定指标;所有KOA患者均在治疗前及治疗后抽取关节液,采用超高效液相色谱仪与主成分分析法(principal components analysis,PCA)分析两组患者治疗前后关节液代谢差异物,并用EZinfo 2.0软件进行PCA潜在差异生物标记物。结果:治疗1个月后,两组患者VAS,WOMAC,自制膝关节肿胀评分均较治疗前有明显改善(P<0.05);治疗1个月后与对照组比较,观察组患者VAS,WOMAC,自制膝关节肿胀评分、综合疗效治疗反应评价均明显升高(P<0.05);与治疗前比较,两组治疗后膝关节关节液中泛酸、犬尿氨酸、酪氨酸表达降低,苯甲酸、柠檬酸及脯氨酸表达升高(P<0.05);与对照组治疗后比较,观察组关节液中泛酸、犬尿氨酸、酪氨酸表达更低,苯甲酸、柠檬酸及脯氨酸表达更高(P<0.05),此外观察组关节液中牛磺酸,β-隐黄素及赖氨酸表达明显升高(P<0.05)。结论:独活寄生汤可减少肝肾亏虚型KOA患者关节疼痛、肿胀程度,增加活动范围,改善KOA患者生活质量;同时随着肝肾亏虚型KOA患者症状的改善,关节液中泛酸、犬尿氨酸、酪氨酸、苯甲酸,柠檬酸,脯氨酸,牛磺酸,β-隐黄素及赖氨酸表达出现变化。

Objective： To observe the clinical efficacy of Duhuo Jisheng Tang in the treatment of liver- and-kidney-deficiency type knee osteoarthritis （KOA）, and analyze the changes in small molecule compounds in synovial fluid before and after treatment with Duhuo Jisheng Tang. Method： A total of 73 patients with KOA diagnosed at the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine were selected and randomly divided into observation group （42 cases） and control group （31 cases）. The observation group was treated with Duhuo Jisheng Tang, 150 mL/time, 2 times a day, for oral administration. The control group was given glucosamine sulfate capsules, 0.5 g/time, 3 times a day, for oral administration. Two groups were treated for a month. Visual analogue scale score （VAS）, Western Ontario and McMaste Universities （WOMAC） , self-made knee joint swelling score and comprehensive therapeutic response were taken as clinical outcome indexes. Synovial fluid of all of the patients with KOA was extracted before and after treatment. Supernatant liquid chromatograph and component analysis were used to analyze the differences in synovial fluid metabolism between two groups before and after treatment. PCA potential difference biomarkers were analyzed by EZinfo 2.0 software. Result： After 1 month of treatment, the scores of VAS, WOMAC and knee swelling of the patients in two groups were significantly alleviated compared with those before treatment （P 〈 0.05）. After 1 month of treatment, compared with control group, VAS, WOMAC, knee swelling score, comprehensive treatment response evaluation in observation group were significantly higher （P 〈 0.05）. Compared with before treatment, in observation group and control group, the levels of pantothenic acid in the knee joint fluid, the expression of tyrosine, tyrosine and the expression of benzoic acid, citric acid and proline were increased after treatment （P 〈 0.05）. Compared with control group, the expressions of pantothenic acid, kynurenine and tyrosine in the synovial fluid in observation group were lower, the expressions of benzoic acid, citric acid and proline were higher （P 〈 0.05 ） , and the expressions of taurine, /3-cryptoxanthin and lysine in synovial fluid of observation group were significantly increased （P 〈 0.05 ）. Conclusion ： Duhuo Jisheng Tang could reduce joint pain, swelling degree, and improve the range of activities and the quality of life of patients with liver-and-kidney-deficiency type KOA. At the same time, the expressions of pantothenic acid, kynnrenine, tyrosine, benzoic acid, citric acid, proline, taurine, β-cryptoxanthin and lysine in synovial fluid were also changed with the improvement of symptoms in liver-and-kidney-deficiency type KOA patients.