[1]王金杰,俞倩丽,朱磊,等.黄精制剂联合塞来昔布胶囊口服治疗膝骨关节炎的临床疗效及其作用机制[J].中医正骨,2018,30(04):32-38,42.
　WANG Jinjie,YU Qianli,ZHU Lei,et al.Clinical curative effect of oral application of polygonatum kingianum preparations and celecoxib capsules on knee osteoarthritis and its mechanism of action[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2018,30(04):32-38,42.
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黄精制剂联合塞来昔布胶囊口服治疗膝骨关节炎的临床疗效及其作用机制()
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《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第30卷
期数:
2018年04期
页码:
32-38,42
栏目:
临床研究
出版日期:
2018-04-20

文章信息/Info

Title:
Clinical curative effect of oral application of polygonatum kingianum preparations and celecoxib capsules on knee osteoarthritis and its mechanism of action
作者:
王金杰1; 俞倩丽1; 朱磊1; 庄汝杰2
1.浙江中医药大学,浙江 杭州 310053; 2.浙江省中医院,浙江 杭州 310006
Author(s):
WANG Jinjie1; YU Qianli1; ZHU Lei1; ZHUANG Rujie2
1.Zhejiang University of Traditional Chinese Medicine,Hangzhou 310053,Zhejiang,China 2.Zhejiang Provincial Hospital of Traditional Chinese Medicine,Hangzhou 310006,Zhejiang,China
关键词:
骨关节炎; 膝;  黄精;  塞来昔布;  白细胞介素1;  白细胞介素33;  基质金属蛋白酶13;  临床试验
Keywords:
Keywords osteoarthritis; knee;  polygonatum kingianum;  celecoxib;  interleukin1;  interleukin33;  matrix metalloproteinase13;  clinical trial
摘要:
目的:观察黄精制剂联合塞来昔布胶囊口服治疗膝骨关节炎的临床疗效及其作用机制。方法:将100例膝骨关节炎患者随机分为2组,每组50例,分别采用单纯塞来昔布胶囊口服、黄精制剂联合塞来昔布胶囊口服治疗。塞来昔布胶囊口服,每日1片,饭后服用; 黄精制剂口服,每日3次,每次2袋,温水冲服; 每隔3周停药1周,1个月为1个疗程,共3个疗程。分别于治疗前及治疗开始后3个月、6个月记录并比较2组患者膝关节疼痛视觉模拟量表(visual analogue scale,VAS)评分、美国膝关节协会评分(American knee society score,KSS)以及白细胞介素1(interleukin,IL)-1、IL-33、基质金属蛋白酶(matrix metalloproteinase,MMP)-13血清含量。结果:黄精制剂联合塞来昔布胶囊组退出5例,单纯塞来昔布胶囊组退出8例。①膝关节疼痛VAS评分。时间因素与分组因素存在交互效应(F=0.451,P=0.038); 2组患者膝关节疼痛VAS评分比较,组间差异有统计学意义,即存在分组效应(t=2.535,P=0.012); 治疗前后不同时间点之间膝关节疼痛VAS评分的差异有统计学意义,即存在时间效应(F=2.193,P=0.025); 2组膝关节疼痛VAS评分随时间均呈降低趋势,但2组的降低趋势不完全一致[(6.36±1.18)分,(6.01±1.16)分,(5.82±1.01)分,F=2.749,P=0.030;(6.43±1.32)分,(6.31±0.96)分,(6.18±1.46)分,F=0.246,P=0.043]; 治疗前和治疗开始后3个月,2组患者膝关节疼痛VAS评分比较,组间差异均无统计学意义(t=1.042,P=0.304; t=1.325,P=0.189); 治疗开始后6个月,黄精制剂联合塞来昔布胶囊组膝关节疼痛VAS评分低于单纯塞来昔布胶囊组(t=2.089,P=0.041)。②KSS膝关节临床评分。时间因素与分组因素存在交互效应(F=7.161,P=0.001); 2组患者KSS膝关节临床评分比较,组间差异有统计学意义,即存在分组效应(t=8.166,P=0.000); 治疗前后不同时间点之间KSS膝关节临床评分的差异有统计学意义,即存在时间效应(F=39.069,P=0.000); 2组患者KSS膝关节临床评分随时间均呈升高趋势,但2组的升高趋势不完全一致[(61.22±2.81)分,(65.07±4.03)分,(67.27±3.49)分,F=40.270,P=0.000;(59.38±2.69)分,(60.21±3.49)分,(62.02±3.88)分,F=7.255,P=0.001]; 治疗前2组患者KSS膝关节临床评分比较,差异无统计学意义(t=3.119,P=0.082); 治疗开始后3个月和6个月黄精制剂联合塞来昔布胶囊组KSS膝关节临床评分均高于单纯塞来昔布胶囊组(t=5.985,P=0.000; t=3.060,P=0.003)。③KSS膝关节日常生活功能评分。时间因素与分组因素存在交互效应(F=1.426,P=0.043)。2组患者KSS膝关节日常生活功能评分比较,组间差异有统计学意义,即存在分组效应(t=4.323,P=0.000); 治疗前后不同时间点之间KSS膝关节日常生活功能评分的差异有统计学意义,即存在时间效应(F=38.648,P=0.000); 2组患者KSS膝关节日常生活功能评分随时间均呈升高趋势,但2组的升高趋势不完全一致[(66.83±2.39)分,(68.31±2.52)分,(71.02±3.66)分,F=39.330,P=0.000;(65.36±2.41)分,(66.90±3.46)分,(68.38±3.83)分,F=9.835,P=0.000]; 治疗前2组患者KSS膝关节日常生活功能评分比较,差异无统计学意义(t=2.849,P=0.054); 治疗开始后3个月和6个月黄精制剂联合塞来昔布胶囊组KSS膝关节日常生活功能评分均高于单纯塞来昔布胶囊组(t=2.176,P=0.032; t=3.289,P=0.001)。④IL-1血清含量。时间因素与分组因素不存在交互效应(F=0.002,P=0.998); 2组患者IL-1血清含量比较,组间差异无统计学意义,即不存在分组效应(t=0.652,P=0.515); 治疗前后不同时间点之间IL-1血清含量的差异有统计学意义,即存在时间效应(F=164.983,P=0.000); 2组患者IL-1血清含量随时间均呈降低趋势,且2组的降低趋势完全一致[(2.85±0.46)ng·L-1,(2.18±0.37)ng·L-1,(2.00±0.48)ng·L-1,F=138.697,P=0.000;(2.79±0.45)ng·L-1,(2.15±0.34)ng·L-1,(1.95±0.08)ng·L-1,F=55.269,P=0.000]。⑤IL-33血清含量。时间因素与分组因素不存在交互效应(F=0.039,P=0.962); 2组患者IL-33血清含量比较,组间差异无统计学意义,即不存在分组效应(t=0.074,P=0.941); 治疗前后不同时间点之间IL-33血清含量的差异有统计学意义,即存在时间效应(F=151.452,P=0.000); 2组患者IL-33血清含量随时间均呈降低趋势,且2组的降低趋势完全一致[(8.68±2.07)ng·L-1,(6.41±1.00)ng·L-1,(5.39±0.82)ng·L-1,F=73.238,P=0.000;(8.84±1.89)ng·L-1,(6.38±1.01)ng·L-1,(5.31±0.78)ng·L-1,F=78.417,P=0.000]。⑥MMP-13血清含量。时间因素与分组因素不存在交互效应 (F=0.017,P=0.983); 2组患者MMP-13血清含量比较,组间差异无统计学意义,即不存在分组效应(t=0.241,P=0.810); 治疗前后不同时间点之间MMP-13血清含量的差异有统计学意义,即存在时间效应(F=76.474,P=0.000); 2组患者MMP-13血清含量随时间均呈降低趋势,且2组的降低趋势完全一致[(2.83±0.97)ng·L-1,(2.02±0.68)ng·L-1,(1.68±0.42)ng·L-1,F=38.634,P=0.000;(2.88±0.98)ng·L-1,(2.06±0.28)ng·L-1,(1.66±0.42)ng·L-1,F=36.189,P=0.000]。结论:黄精制剂联合塞来昔布胶囊口服与单纯塞来昔布胶囊口服治疗KOA,均能缓解膝关节疼痛和改善膝关节功能,但前者的疗效优于后者; 其作用机制可能与其能降低血清中IL-1、IL-33及MMP-13的含量有关。
Abstract:
ABSTRACT Objective:To observe the clinical curative effect of oral application of polygonatum kingianum preparations and celecoxib capsules on knee osteoarthritis(KOA)and to study its mechanism of action.Methods:One hundred patients with KOA were randomly divided into 2 groups,50 cases in each group,and were treated with monotherapy of oral application of celecoxib capsules(monotherapy group)and combination therapy of oral application of polygonatum kingianum preparations and celecoxib capsules(combination therapy group)respectively.The celecoxib capsules were taken after meal,one tablet a day.The polygonatum kingianum preparations were taken after mixing with warm water,three times a day,2 bags at a time.Both celecoxib capsules and polygonatum kingianum preparations were taken for consecutive 3 courses of treatment,1 month for each course with a 1-week rest-insertion between courses.The knee pain visual analogue scale(VAS)score,the American knee society score(KSS)and the serum contents of interleukin(IL)-1,IL-33 and matrix metalloproteinase(MMP)-13 were recorded and compared between the 2 groups before treatment and at 3 and 6 months after the beginning of the treatment respectively.Results:Five patients in combination therapy group and 8 patients in monotherapy group dropped out of the study.There was interaction between time factor and group factor in knee pain VAS scores(F=0.451,P=0.038).There was statistical difference in the knee pain VAS scores between the 2 groups,in other words,there was group effect(t=2.535,P=0.012).There was statistical difference in knee pain VAS scores between different timepoints before and after the treatment,in other words,there was time effect(F=2.193,P=0.025).The knee pain VAS scores presented a time-dependent decreasing trend in both of the 2 groups,while the 2 groups were inconsistent with each other in the decreasing trend of knee pain VAS scores(6.36+/-1.18,6.01+/-1.16,5.82+/-1.01 points,F=2.749,P=0.030; 6.43+/-1.32,6.31+/-0.96,6.18+/-1.46 points,F=0.246,P=0.043).There was no statistical difference in knee pain VAS scores between the 2 groups before the treatment and at 3 months after the beginning of the treatment(t=1.042,P=0.304; t=1.325,P=0.189).The knee pain VAS scores were lower in combination therapy group compared to monotherapy group at 6 months after the beginning of the treatment(t=2.089,P=0.041).There was interaction between time factor and group factor in KSS clinical scores(F=7.161,P=0.001).There was statistical difference in KSS clinical scores between the 2 groups,in other words,there was group effect(t=8.166,P=0.000).There was statistical difference in KSS clinical scores between different timepoints before and after the treatment,in other words,there was time effect(F=39.069,P=0.000).The KSS clinical scores presented a time-dependent increasing trend in both of the 2 groups,while the 2 groups were inconsistent with each other in the increasing trend of KSS clinical scores(61.22+/-2.81,65.07+/-4.03,67.27+/-3.49 points,F=40.270,P=0.000; 59.38+/-2.69,60.21+/-3.49,62.02+/-3.88 points,F=7.255,P=0.001).There was no statistical difference in KSS clinical scores between the 2 groups before the treatment(t=3.119,P=0.082).The KSS clinical scores were higher in combination therapy group compared to monotherapy group at 3 and 6 months after the beginning of the treatment(t=5.985,P=0.000; t=3.060,P=0.003).There was interaction between time factor and group factor in KSS activity of daily living(ADL)scores(F=1.426,P=0.043).There was statistical difference in KSS ADL scores between the 2 groups,in other words,there was group effect(t=4.323,P=0.000).There was statistical difference in KSS ADL scores between different timepoints before and after the treatment,in other words,there was time effect(F=38.648,P=0.000).The KSS ADL scores presented a time-dependent increasing trend in both of the 2 groups,while the 2 groups were inconsistent with each other in the increasing trend of KSS ADL scores(66.83+/-2.39,68.31+/-2.52,71.02+/-3.66 points,F=39.330,P=0.000; 65.36+/-2.41,66.90+/-3.46,68.38+/-3.83 points,F=9.835,P=0.000).There was no statistical difference in KSS ADL scores between the 2 groups before the treatment(t=2.849,P=0.054).The KSS ADL scores were higher in combination therapy group compared to monotherapy group at 3 and 6 months after the beginning of the treatment(t=2.176,P=0.032; t=3.289,P=0.001).There was no interaction between time factor and group factor in the serum content of IL-1(F=0.002,P=0.998).There was no statistical difference in the serum content of IL-1 between the 2 groups,in other words,there was no group effect(t=0.652,P=0.515).There was statistical difference in serum content of IL-1 between different timepoints before and after the treatment,in other words,there was time effect(F=164.983,P=0.000).The serum content of IL-1 presented a time-dependent decreasing trend in both of the 2 groups,while the 2 groups were consistent with each other in the decreasing trend of serum content of IL-1(2.85+/-0.46,2.18+/-0.37,2.00+/-0.48 ng/L,F=138.697,P=0.000; 2.79+/-0.45,2.15+/-0.34,1.95+/-0.08 ng/L,F=55.269,P=0.000).There was no interaction between time factor and group factor in the serum content of IL-33(F=0.039,P=0.962).There was no statistical difference in the serum content of IL-33 between the 2 groups,in other words,there was no group effect(t=0.074,P=0.941).There was statistical difference in serum content of IL-33 between different timepoints before and after the treatment,in other words,there was time effect(F=151.452,P=0.000).The serum content of IL-33 presented a time-dependent decreasing trend in both of the 2 groups,while the 2 groups were consistent with each other in the decreasing trend of serum content of IL-33(8.68+/-2.07,6.41+/-1.00,5.39+/-0.82 ng/L,F=73.238,P=0.000; 8.84+/-1.89,6.38+/-1.01,5.31+/-0.78 ng/L,F=78.417,P=0.000).There was no interaction between time factor and group factor in the serum content of MMP-13(F=0.017,P=0.983).There was no statistical difference in the serum content of MMP-13 between the 2 groups,in other words,there was no group effect(t=0.241,P=0.810).There was statistical difference in serum content of MMP-13 between different timepoints before and after the treatment,in other words,there was time effect(F=76.474,P=0.000).The serum content of MMP-13 presented a time-dependent decreasing trend in both of the 2 groups,while the 2 groups were consistent with each other in the decreasing trend of serum content of MMP-13(2.83+/-0.97,2.02+/-0.68,1.68+/-0.42 ng/L,F=38.634,P=0.000; 2.88+/-0.98,2.06+/-0.28,1.66+/-0.42 ng/L,F=36.189,P=0.000).Conclusion:Both the combination therapy of oral application of polygonatum kingianum preparations and celecoxib capsules and the monotherapy of oral application of celecoxib capsules can relieve the knee pain and improve the knee function in the treatment of KOA,however,the former is better than the latter in curative effect and it can reduce the serum contents of IL-1,IL-33 and MMP-13,which may be the mechanisms of action.

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备注/Memo

备注/Memo:
基金项目:2014年浙江省重大科技专项计划(2014C03038); 2016年浙江省中医药科技计划项目(2016ZA085) 通讯作者:庄汝杰 E-mail:rujiezhuang@163.com
更新日期/Last Update: 2018-08-24