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[1]帥波,沈霖,楊艷萍,等.加味青娥丸治療膝骨關(guān)節(jié)炎的作用機制研究[J].中醫(yī)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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加味青娥丸治療膝骨關(guān)節(jié)炎的作用機制研究()
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《中醫(yī)正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第27卷
期數(shù):
2015年07期
頁碼:
15-21
欄目:
膝骨關(guān)節(jié)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:
帥波沈霖楊艷萍徐曉娟馬陳呂林夏雪
華中科技大學(xué)同濟醫(yī)學(xué)院附屬協(xié)和醫(yī)院,湖北 武漢 430022
Author(s):
SHUAI BoSHEN LinYANG YanpingXU XiaojuanMA ChenLV LinXIA Xue
Wuhan Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology,Wuhan 430022,Hubei,China
關(guān)鍵詞:
骨關(guān)節(jié)炎 青娥丸 白細胞介素1β 腫瘤壞死因子α 一氧化氮 基質(zhì)金屬蛋白酶-3 治療臨床研究性
Keywords:
osteoarthritisknee Qinge pill interleukin-1beta tumor necrosis factor-alpha nitric oxide matrix metalloproteinase 3 therapiesinvestigational
摘要:
目的:探討加味青娥丸治療膝骨關(guān)節(jié)炎(knee osteoarthritis,KOA)的作用機制。方法:將符合要求的120例KOA患者隨機分為加味青娥丸組和芍藥丸組,每組60例; 分別口服加味青娥丸和芍藥丸,每次1丸,每天3次,連續(xù)服用12周。服藥期間2組患者均進行患肢皮膚牽引及不負重功能鍛煉。當患者關(guān)節(jié)疼痛不能緩解或加重,無法忍受時,給予塞來昔布膠囊,每次1粒,每天1次,疼痛控制后立即停止服用塞來昔布膠囊。分別于治療前和治療12周后測定2組患者的膝關(guān)節(jié)疼痛視覺模擬評分(visual analogue score,VAS)和西安大略和麥克馬斯特大學(xué)(Western Ontario and McMaster Universities,WOMAC)骨關(guān)節(jié)炎指數(shù)評分,并測定患者血清白細胞介素-1β(interleukin-1β,IL-1β)、腫瘤壞死因子α(tumor necrosis factor-α,TNF-α)和一氧化氮(nitric oxide,NO)水平,以及外周血單核細胞(peripheral blood mononuclear cell,PBMC)基質(zhì)金屬蛋白酶-3 mRNA(matrix metalloproteinase-3 mRNA,MMP-3 mRNA)表達水平。結(jié)果:①膝關(guān)節(jié)疼痛VAS評分及WOMAC評分。治療前2組患者膝關(guān)節(jié)疼痛VAS評分及WOMAC評分比較,組間差異均無統(tǒng)計學(xué)意義(t=0.626,P=0.553; t=0.856,P=0.394); 治療12周后芍藥丸組膝關(guān)節(jié)疼痛VAS評分及WOMAC評分均高于加味青娥丸組(t=9.075,P=0.000; t=17.149,P=0.000)。治療12周后加味青娥丸組膝關(guān)節(jié)疼痛VAS評分及WOMAC評分均較治療前降低(t=10.392,P=0.000; t=19.075,P=0.000); 芍藥丸組膝關(guān)節(jié)疼痛VAS評分及WOMAC評分治療前后比較,差異均無統(tǒng)計學(xué)意義(t=0.664,P=0.508; t=1.860,P=0.065)。②血清IL-1β水平。治療前2組各級別患者血清IL-1β水平比較,差異無統(tǒng)計學(xué)意義(F=0.612,P=0.894)。治療12周后加味青娥丸組患者血清IL-1β水平與治療前相比,差異有統(tǒng)計學(xué)意義(F=16.986,P=0.000); Ⅰ、Ⅱ級患者血清IL-1β水平較治療前降低(P=0.000; P=0.000),Ⅲ、Ⅳ級患者血清IL-1β水平與治療前相比,差異均無統(tǒng)計學(xué)意義(P=0.075; P=0.161)。治療12周后芍藥丸組各級別患者血清IL-1β水平與治療前相比,差異無統(tǒng)計學(xué)意義(F=0.651,P=0.885)。治療12周后2組患者血清IL-1β水平比較,差異有統(tǒng)計學(xué)意義(F=3.881,P=0.044); 加味青娥丸組Ⅰ、Ⅱ級患者血清IL-1β水平均低于芍藥丸組(P=0.008; P=0.000); 2組Ⅲ、Ⅳ級患者血清IL-1β水平比較,組間差異無統(tǒng)計學(xué)意義(P=0.342; P=0.444)。③血清TNF-α水平。治療前2組各級別患者血清TNF-α水平比較,差異無統(tǒng)計學(xué)意義(F=1.447,P=0.695)。治療12周后加味青娥丸組患者血清TNF-α水平與治療前相比,差異有統(tǒng)計學(xué)意義(F=103.189,P=0.000); Ⅰ、Ⅱ級患者血清TNF-α水平較治療前降低(P=0.000; P=0.000),Ⅲ、Ⅳ級患者血清TNF-α水平與治療前相比,差異均無統(tǒng)計學(xué)意義(P=0.281; P=0.079)。治療12周后芍藥丸組各級別患者血清TNF-α水平與治療前相比,差異無統(tǒng)計學(xué)意義(F=1.065,P=0.786)。治療12周后2組患者血清TNF-α水平比較,差異有統(tǒng)計學(xué)意義(F=13.958,P=0.003); 加味青娥丸組Ⅰ、Ⅱ、Ⅳ級患者血清TNF-α水平均低于芍藥丸組(P=0.000; P=0.000; P=0.018); 2組Ⅲ級患者血清TNF-α水平比較,差異無統(tǒng)計學(xué)意義(P=0.125)。④血清NO水平。治療前2組各級別患者血清NO水平比較,差異無統(tǒng)計學(xué)意義(F=0.505,P=0.918)。治療12周后加味青娥丸組患者血清NO水平與治療前相比,差異有統(tǒng)計學(xué)意義(F=25.740,P=0.000); Ⅰ、Ⅱ級患者血清NO水平較治療前降低(P=0.000; P=0.000),Ⅲ、Ⅳ級患者血清NO水平與治療前相比,差異均無統(tǒng)計學(xué)意義(P=0.080; P=0.121)。治療12周后芍藥丸組各級別患者血清NO水平與治療前相比,差異無統(tǒng)計學(xué)意義(F=0.427,P=0.935)。治療12周后2組患者血清NO水平比較,差異有統(tǒng)計學(xué)意義(F=5.621,P=0.039); 加味青娥丸組Ⅰ、Ⅱ級患者血清NO水平均低于芍藥丸組(P=0.000; P=0.000); 2組Ⅲ、Ⅳ級患者血清NO水平比較,組間差異無統(tǒng)計學(xué)意義(P=0.062; P=0.226)。⑤PBMC MMP-3 mRNA水平。治療前及治療12周后,2組各級別患者PBMC MMP-3 mRNA水平比較,組間差異均無統(tǒng)計學(xué)意義(F=0.002,P=0.999; F=0.033,P=0.998)。治療12周后加味青娥丸組和芍藥丸組各級別患者MMP-3 mRNA水平與治療前相比,差異均無統(tǒng)計學(xué)意義(F=0.029,P=0.999; F=0.002,P=0.999)。結(jié)論:加味青娥丸治療早中期KOA的機理之一可能是通過各種途徑下調(diào)血清IL-1β、TNF-α及NO水平,從而抑制軟骨細胞凋亡和軟骨基質(zhì)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(芍藥丸,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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備注/Memo

備注/Memo:
2015-04-15收稿 2015-05-27修回
基金項目:國家自然科學(xué)基金項目(81273907,81403257)
通訊作者:沈霖 E-mail:[email protected]
更新日期/Last Update: 2015-07-30