消瘀散软膏外敷联合臭氧关节腔注射治疗膝骨关节炎

A combination therapy of external application of Xiaoyu San( 消瘀散) ointment and intra-articular injection of ozone for the treatment of knee osteoarthritis

目的:探讨消瘀散软膏外敷联合臭氧关节腔注射治疗膝骨关节炎的临床疗效和安全性。方法:膝骨关节炎患者120例,随机分为3组,每组40例。联合治疗组采用消瘀散软膏外敷联合臭氧关节腔注射治疗,消瘀散组单纯采用消瘀散软膏外敷治疗,臭氧组单纯采用臭氧关节腔注射治疗;共治疗3周。分别于治疗前、治疗1周后及治疗3周后采用疼痛视觉模拟评分法(visual analogue scale,VAS)、美国西安大略和麦克马斯特大学骨关节炎指数评分(the western Ontario and Mc Master universities osteoarthritis index,WOMAC)及Lequesne和Mery膝关节骨性关节炎严重度指数评分,对患膝疼痛及功能情况进行评价;治疗3周后,参照《中药新药治疗骨性关节炎的临床研究指导原则》疗效评定标准评价疗效;并在治疗期间观察有无与治疗相关的不良反应,检测血、尿常规及肝肾功能。结果:治疗前后各时间点间患膝VAS评分比较,差异有统计学意义,存在时间效应(F=76.212,P=0.000);3组患者间患膝VAS评分比较,差异有统计学意义,存在分组效应(F=15.669,P=0.000);治疗前,3组患者间患膝VAS评分比较,差异无统计学意义[(7.81±0.84)分,(8.02±0.71)分,(7.65±0.55)分;F=0.472,P=0.697];治疗1周后和治疗3周后,联合治疗组患膝VAS评分低于消瘀散组和臭氧组[(3.30±0.45)分,(5.87±0.84)分,(5.73±0.67)分,F=20.033,P=0.000;(1.84±0.84)分,(4.82±0.43)分,(4.23±0.45)分;F=25.210,P=0.000]。时间因素与分组因素存在交互效应(F=43.220,P=0.041)。治疗前后各时间点间患膝WOMAC评分比较,差异有统计学意义,存在时间效应(F=28.302,P=0.028);3组患者间患膝WOMAC评分比较,差异有统计学意义,存在分组效应(F=12.892,P=0.001);治疗前,3组患者间患膝WOMAC评分比较,差异无统计学意义[(141.81±8.22)分,(149.24±14.32)分,(145.56±10.37)分;F=0.750,P=0.493];治疗1周后和治疗3周后,联合治疗组患膝WOMAC评分低于消瘀散组和臭氧组[(115.21±4.18)分,(128.34±10.37)分,(120.89±12.28)分,F=12.896,P=0.001;(74.17±10.84)分,(97.28±7.91)分,(81.32±12.34)分,F=20.872,P=0.000];时间因素和分组因素之间存在交互效应(F=4.698,P=0.006)。治疗前后各时间点间患膝Lequesne评分比较,差异有统计学意义,存在时间效应(F=30.302,P=0.031);3组患者间患膝Lequesne评分比较,差异有统计学意义,存在分组效应(F=8.892,P=0.012);治疗前,3组患者间患膝Lequesne评分比较,差异无统计学意义[(17.94±2.97)分,(16.74±2.68)分,(16.38±2.72)分;F=0.452,P=0.587];治疗1周后和治疗3周后,联合治疗组患膝Lequesne评分低于消瘀散组和臭氧组[(8.61±3.05)分,(12.28±2.65)分,(10.80±2.68)分,F=5.371,P=0.021;(3.23±1.92)分,(8.68±2.17)分,(5.48±2.39)分;F=4.246,P=0.037];时间因素和分组因素之间存在交互效应(F=40.176,P=0.010)。治疗3周后,联合治疗组临床控制6例、显效17例、有效16例、无效1例,消瘀散组临床控制1例、显效12例、有效21例、无效6例,臭氧组临床控制2例、显效11例、有效24例、无效3例,联合治疗组临床疗效优于消瘀散组和臭氧组(R联合治疗组=48.18,R消瘀散组=68.30,R臭氧组=65.02;χ2=9.281,P=0.010)。3组患者治疗期间均未出现皮疹、恶心、呕吐等不良反应,血、尿常规及肝肾功能检查均正常。结论:消瘀散软膏外敷联合臭氧关节腔注射治疗膝骨关节炎,可有效缓解症状、改善关节功能,疗效优于单纯消瘀散外敷和单纯臭氧注射,且安全可靠。

Objective：To explore the clinical curative effects and safety of external application of Xiaoyu San（消瘀散）ointment com-bined with intra-articular injection of ozone in the treatment of knee osteoarthritis（KOA）.Methods：One hundred and twenty patients with KOA were randomly divided into 3 groups,40 cases in each group.The patients were treated with external application of Xiaoyu San oint-ment combined with intra-articular injection of ozone（combination therapy group）external application of Xiaoyu San ointment（Xiaoyu San group）and intra-articular injection of ozone（ozone group）respectively for 3 weeks.The pain degree and function of knee were evaluated by using the visual analogue scale（VAS）,the western Ontario and McMaster universities osteoarthritis index（WOMAC）and Lequesne and Mery knee osteoarthritis severity index before the treatment and at 1 and 3 weeks after the treatment respectively.The curative effects were evaluated according to the criterion in Guiding principles ofclinical research on new Chinese medicine for osteoarthritis.The treatment-related adverse reactions were observed,meanwhile,the blood RT,urine RT,and hepatorenal function were examined.Results：There was statistical difference in knee VAS scores between different time points（F=76.212,P=0.000）and between different groups（F=15.669,P=0.000）,in other words,there was time effect and grouping effect.There was no statistical difference in knee VAS scores between the three groups before the treatment（7.81 ＋/-0.84,8.02＋/-0.71 ,7.65 ＋/-0.55 points;F=0.472,P=0.697）.The VAS scores were lower in the combination therapy group compared to the Xiaoyu San group and ozone group after 1 -week treatment and 3 -week treatment （3.30＋/-0.45,5.87＋/-0.84,5.73＋/-0.67 points;F=20.033,P=0.000;1 .84＋/-0.84,4.82＋/-0.43,4.23＋/-0.45 points;F=25.21 0,P=0.000）.There was interaction between time factor and grouping factor（F=43.220,P=0.041 ）.There was statistical differ-ence in knee WOMAC scores between different time points,in other words,there was time effect（F=28.302,P=0.028）.There was statis-tical difference in knee WOMAC scores between the three groups,in other words,there was grouping effect（F=1 2.892,P=0.001 ）.There was no statistical difference in knee WOMAC scores between the three groups before the treatment（1 41 .81 ＋/-8.22,1 49.24＋/-1 4.32, 1 45.56＋/-1 0.37 points;F=0.750,P=0.493）.The WOMAC scores were lower in the combination therapy group compared to the Xi-aoyu San group and ozone group after 1 -week treatment and 3-week treatment（1 1 5.21 ＋/-4.1 8,1 28.34＋/-1 0.37,1 20.89＋/-1 2.28 points,F=1 2.896,P=0.001;74.1 7＋/-1 0.84,97.28＋/-7.91 ,81 .32＋/-1 2.34 points,F=20.872,P=0.000）.There was interaction between time factor and grouping factor（F=4.698,P=0.006）.There was statistical difference in knee Lequesne scores between different time points,in other words,there was time effect（F=30.302,P=0.031 ）.There was statistical difference in knee Lequesne scores between the three groups,in other words,there was grouping effect（F=8.892,P=0.01 2）.There was no statistical difference in knee Lequesne scores between the three groups before the treatment（1 7.94＋/-2.97,1 6.74＋/-2.68,1 6.38 ＋/-2.72 points;F=0.452,P=0.587）. The Lequesne scores were lower in the combination therapy group compared to the Xiaoyu San group and ozone group after 1 -week treat-ment and 3-week treatment（8.61 ＋/-3.05,1 2.28 ＋/-2.65,1 0.80 ＋/-2.68 points,F=5.371 ,P=0.021;3.23 ＋/-1 .92,8.68 ＋/-2.17,5.48＋/-2.39 points;F=4.246,P=0.037）.There was interaction between time factor and grouping factor（F=40.176,P=0.01 0）.After 3-week treatment,6 patients were clinical controlled,1 7 good,1 6 fair and 1 poor in the combination therapy group;and 1 patients were clinical controlled,1 2 good,21 fair and 6 poor in the Xiaoyu San group;while 2 patients were clinical controlled,1 1 good,24 fair and 3 poor in the ozone group.The combination therapy group surpassed the Xiaoyu San group and ozone group in the clinical curative effect（Rcombination therapy group =48.1 8,RXiaoyu San group =68.30,Rozone group =65.02;χ^2 =9.281 ,P=0.01 0）.No adverse reactions including skin rash,nausea and vomitingr were found;and the blood RT,urine RT,and hepatorenal function were normal.Conclusion：The combination therapy of external application of Xiaoyu San ointment and intra-articular injection of ozone can effectively relieve the symptoms and improve the knee function in the treatment of KOA,and its curative effect is better than that of monotherapy of external application of Xiaoyu San ointment and intra-articular injection of ozone,and it is safe for treatment of KOA.