[1]帅波,沈霖,杨艳萍,等.加味青娥丸治疗膝骨关节炎的作用机制研究[J].中医正骨,2015,27(07):15-21.
　SHUAI Bo,SHEN Lin,YANG Yanping,et al.Study on the mechanism of action of Jiawei Qing'e Wan(加味青娥丸)for the treatment of knee osteoarthritis[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2015,27(07):15-21.
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加味青娥丸治疗膝骨关节炎的作用机制研究()
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《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第27卷
期数:
2015年07期
页码:
15-21
栏目:
膝骨关节炎
出版日期:
2015-07-31

文章信息/Info

Title:
Study on the mechanism of action of Jiawei Qing'e Wan(加味青娥丸)for the treatment of knee osteoarthritis
作者:
帅波; 沈霖; 杨艳萍; 徐晓娟; 马陈; 吕林; 夏雪
华中科技大学同济医学院附属协和医院,湖北 武汉 430022
Author(s):
SHUAI Bo; SHEN Lin; YANG Yanping; XU Xiaojuan; MA Chen; LV Lin; XIA Xue
Wuhan Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology,Wuhan 430022,Hubei,China
关键词:
骨关节炎; 膝;  青娥丸;  白细胞介素1β;  肿瘤坏死因子α;  一氧化氮;  基质金属蛋白酶-3;  治疗; 临床研究性
Keywords:
osteoarthritis; knee;  Qinge pill;  interleukin-1beta;  tumor necrosis factor-alpha;  nitric oxide;  matrix metalloproteinase 3;  therapies; investigational
摘要:
目的:探讨加味青娥丸治疗膝骨关节炎(knee osteoarthritis,KOA)的作用机制。方法:将符合要求的120例KOA患者随机分为加味青娥丸组和芍药丸组,每组60例; 分别口服加味青娥丸和芍药丸,每次1丸,每天3次,连续服用12周。服药期间2组患者均进行患肢皮肤牵引及不负重功能锻炼。当患者关节疼痛不能缓解或加重,无法忍受时,给予塞来昔布胶囊,每次1粒,每天1次,疼痛控制后立即停止服用塞来昔布胶囊。分别于治疗前和治疗12周后测定2组患者的膝关节疼痛视觉模拟评分(visual analogue score,VAS)和西安大略和麦克马斯特大学(Western Ontario and McMaster Universities,WOMAC)骨关节炎指数评分,并测定患者血清白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和一氧化氮(nitric oxide,NO)水平,以及外周血单核细胞(peripheral blood mononuclear cell,PBMC)基质金属蛋白酶-3 mRNA(matrix metalloproteinase-3 mRNA,MMP-3 mRNA)表达水平。结果:①膝关节疼痛VAS评分及WOMAC评分。治疗前2组患者膝关节疼痛VAS评分及WOMAC评分比较,组间差异均无统计学意义(t=0.626,P=0.553; t=0.856,P=0.394); 治疗12周后芍药丸组膝关节疼痛VAS评分及WOMAC评分均高于加味青娥丸组(t=9.075,P=0.000; t=17.149,P=0.000)。治疗12周后加味青娥丸组膝关节疼痛VAS评分及WOMAC评分均较治疗前降低(t=10.392,P=0.000; t=19.075,P=0.000); 芍药丸组膝关节疼痛VAS评分及WOMAC评分治疗前后比较,差异均无统计学意义(t=0.664,P=0.508; t=1.860,P=0.065)。②血清IL-1β水平。治疗前2组各级别患者血清IL-1β水平比较,差异无统计学意义(F=0.612,P=0.894)。治疗12周后加味青娥丸组患者血清IL-1β水平与治疗前相比,差异有统计学意义(F=16.986,P=0.000); Ⅰ、Ⅱ级患者血清IL-1β水平较治疗前降低(P=0.000; P=0.000),Ⅲ、Ⅳ级患者血清IL-1β水平与治疗前相比,差异均无统计学意义(P=0.075; P=0.161)。治疗12周后芍药丸组各级别患者血清IL-1β水平与治疗前相比,差异无统计学意义(F=0.651,P=0.885)。治疗12周后2组患者血清IL-1β水平比较,差异有统计学意义(F=3.881,P=0.044); 加味青娥丸组Ⅰ、Ⅱ级患者血清IL-1β水平均低于芍药丸组(P=0.008; P=0.000); 2组Ⅲ、Ⅳ级患者血清IL-1β水平比较,组间差异无统计学意义(P=0.342; P=0.444)。③血清TNF-α水平。治疗前2组各级别患者血清TNF-α水平比较,差异无统计学意义(F=1.447,P=0.695)。治疗12周后加味青娥丸组患者血清TNF-α水平与治疗前相比,差异有统计学意义(F=103.189,P=0.000); Ⅰ、Ⅱ级患者血清TNF-α水平较治疗前降低(P=0.000; P=0.000),Ⅲ、Ⅳ级患者血清TNF-α水平与治疗前相比,差异均无统计学意义(P=0.281; P=0.079)。治疗12周后芍药丸组各级别患者血清TNF-α水平与治疗前相比,差异无统计学意义(F=1.065,P=0.786)。治疗12周后2组患者血清TNF-α水平比较,差异有统计学意义(F=13.958,P=0.003); 加味青娥丸组Ⅰ、Ⅱ、Ⅳ级患者血清TNF-α水平均低于芍药丸组(P=0.000; P=0.000; P=0.018); 2组Ⅲ级患者血清TNF-α水平比较,差异无统计学意义(P=0.125)。④血清NO水平。治疗前2组各级别患者血清NO水平比较,差异无统计学意义(F=0.505,P=0.918)。治疗12周后加味青娥丸组患者血清NO水平与治疗前相比,差异有统计学意义(F=25.740,P=0.000); Ⅰ、Ⅱ级患者血清NO水平较治疗前降低(P=0.000; P=0.000),Ⅲ、Ⅳ级患者血清NO水平与治疗前相比,差异均无统计学意义(P=0.080; P=0.121)。治疗12周后芍药丸组各级别患者血清NO水平与治疗前相比,差异无统计学意义(F=0.427,P=0.935)。治疗12周后2组患者血清NO水平比较,差异有统计学意义(F=5.621,P=0.039); 加味青娥丸组Ⅰ、Ⅱ级患者血清NO水平均低于芍药丸组(P=0.000; P=0.000); 2组Ⅲ、Ⅳ级患者血清NO水平比较,组间差异无统计学意义(P=0.062; P=0.226)。⑤PBMC MMP-3 mRNA水平。治疗前及治疗12周后,2组各级别患者PBMC MMP-3 mRNA水平比较,组间差异均无统计学意义(F=0.002,P=0.999; F=0.033,P=0.998)。治疗12周后加味青娥丸组和芍药丸组各级别患者MMP-3 mRNA水平与治疗前相比,差异均无统计学意义(F=0.029,P=0.999; F=0.002,P=0.999)。结论:加味青娥丸治疗早中期KOA的机理之一可能是通过各种途径下调血清IL-1β、TNF-α及NO水平,从而抑制软骨细胞凋亡和软骨基质降解。
Abstract:
Objective:To explore the mechanism of action of Jiawei Qing'e Wan(加味青娥丸,JWQEW)for the treatment of knee osteoarthritis(KOA).Methods:One hundred and twenty patients with KOA were randomly divided into two groups,60 cases in each group.The patients were treated with JWQEW and Shaoyao Wan(芍药丸,SYW)respectively,one pill 3 times a day for consecutive 12 weeks.All cases received skin traction and non-weight-bearing functional exercise in affected limbs during the treatment,and those patients who suffered from unrelieved or aggravated knee pain were given Celecoxib capsules,1 pill once a day.Celecoxib capsules would be withdrew as long as the knee pain was controlled.The knee pain visual analogue score(VAS)and Western Ontario and McMaster Universities(WOMAC)osteoarthritis index scores were evaluated before the treatment and after 12-week treatment respectively.The serum level of IL-1β,TNF-α and NO and the expression of PBMC MMP-3 mRNA were also detected at the same time.Results:There were no statistical differences in knee pain VAS scores and WOMAC scores between the two groups before the treatment(t=0.626,P=0.553; t=0.856,P=0.394).After 12-week treatment,the knee VAS scores and WOMAC scores were higher in SYW group compared to JWQEW group(t=9.075,P=0.000; t=17.149,P=0.000).After 12-week treatment,the knee VAS scores and WOMAC scores decreased in JWQEW group(t=10.392,P=0.000; t=19.075,P=0.000).There were no statistical differences between pretreatment and post-treatment in knee VAS scores and WOMAC scores in SYW group(t=0.664,P=0.508; t=1.860,P=0.065).There was no statistical difference in the serum level of IL-1β between the 2 groups before the treatment(F=0.612,P=0.894).After 12-week treatment,there was statistical difference in the serum level of IL-1β in JWQEW group between pretreatment and post-treatment(F=16.986,P=0.000).The serum level of IL-1β decreased after the treatment in gradeⅠandⅡcases(P=0.000,P=0.000),while there was no statistical difference in serum level of IL-1β between pretreatment and post-treatment in gradeⅢandⅣcases(P=0.075,P=0.161).After 12-week treatment,there was no statistical difference in the serum level of IL-1β in SYW group between pretreatment and post-treatment(F=0.651,P=0.885).There was statistical difference in the serum level of IL-1β between the 2 groups after the treatment(F=3.881,P=0.044).The serum IL-1β level was lower in JWQEW group compared to SYW Group in gradeⅠandⅡcases(P=0.008,P=0.000),while there was no statistical difference in the serum IL-1β level in gradeⅢandⅣcases between the 2 groups(P=0.342,P=0.444).There was no statistical difference in the serum level of TNF-α between the 2 groups before the treatment(F=1.447,P=0.695).After 12-week treatment,there was statistical difference in the serum level of TNF-α in JWQEW group between pretreatment and post-treatment(F=103.189,P=0.000).The serum level of TNF-α decreased in gradeⅠandⅡcases after the treatment(P=0.000; P=0.000),while no statistical difference was found in gradeⅢandⅣcases(P=0.281,P=0.079).After 12-week treatment,there was no statistical difference in the serum level of TNF-α in SYW group between pretreatment and post-treatment(F=1.065,P=0.786)and there was statistical difference between the two groups(F=13.958,P=0.003).The serum level of TNF-α was lower in gradeⅠ,Ⅱ,andⅣcases in JWQEW group compared to SYW group(P=0.000,P=0.000,P=0.018),while there was no statistical difference in gradeⅢcases between the 2 groups(P=0.125).There was no statistical difference in the serum level of NO between the 2 groups before the treatment(F=0.505,P=0.918).There was statistical difference in the serum level of NO in JWQEW group between pretreatment and post-treatment(F=25.740,P=0.000).The serum level of NO decreased in gradeⅠandⅡcases after the treatment(P=0.000,P=0.000),while there was no statistical difference between pretreatment and post-treatment in gradeⅢandⅣcases(P=0.080,P=0.121).After 12-weeks treatment,there was no statistical difference between pretreatment and post-treatment in serum NO level in all grades of cases in SYW group(F=0.427,P=0.935).There was significant difference in the serum level of NO between the two groups after 12-week treatment(F=5.621,P=0.039).The serum level of NO was lower in gradeⅠandⅡcases in JWQEW group compared to SYW group(P=0.000,P=0.000),while there was no statistical difference in gradeⅢandⅣcases between the 2 groups(P=0.062,P=0.226).There was no statistical difference in the expression level of PBMC MMP-3 mRNA between the two groups before the treatment and after 12-week treatment(F=0.002,P=0.999; F=0.033,P=0.998).There was no statistical difference in the expression level of PBMC MMP-3 mRNA between pretreatment and post-treatment in both of the two groups(F=0.029,P=0.999; F=0.002,P=0.999).Conclusion:By down-regulating the serum levels of IL-1β,TNF-α and NO through various pathways,JWQEW can inhibit cartilage cell apoptosis and cartilage matrix degradation,which may be one of the mechanisms of action for treatment of early-middle KOA.

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备注/Memo

备注/Memo:
2015-04-15收稿 2015-05-27修回
基金项目:国家自然科学基金项目(81273907,81403257)
通讯作者:沈霖 E-mail:shenlinhb@sina.cn
更新日期/Last Update: 2015-07-30