具紫勇,王穎,陳昌樂(lè),崔花順,丁佳燕,王珂

(1.上海中醫(yī)藥大學(xué),上海 201203;2.上海市氣功研究所,上海 200030;3.上海中醫(yī)藥大學(xué)附屬曙光醫(yī)院,上海201203)

電針治療膝骨關(guān)節(jié)炎臨床研究

具紫勇1,王穎1,陳昌樂(lè)2,崔花順3,丁佳燕1,王珂3

(1.上海中醫(yī)藥大學(xué),上海 201203;2.上海市氣功研究所,上海 200030;3.上海中醫(yī)藥大學(xué)附屬曙光醫(yī)院,上海201203)

目的 觀察電針治療膝骨關(guān)節(jié)炎的臨床療效。方法 將60例膝骨關(guān)節(jié)炎患者采用隨機(jī)數(shù)字表法隨機(jī)分為治療組和對(duì)照組,每組30例。對(duì)照組給予塞來(lái)昔布膠囊口服治療,治療組給予電針治療。14 d為1個(gè)療程。觀察兩組血清相關(guān)細(xì)胞因子(apelin、TNFα、TNFsR-Ⅰ、TNFsR-Ⅱ、IL-1β和IL-6)水平和治療前后WOMAC骨關(guān)節(jié)炎評(píng)分、視覺(jué)模擬評(píng)分(VAS)的變化情況。結(jié)果 兩組治療前后WOMAC骨關(guān)節(jié)炎評(píng)分在總評(píng)分、疼痛、僵硬、功能障礙方面差異均有統(tǒng)計(jì)學(xué)意義(P＜0.05);兩組治療后WOMAC總評(píng)分、僵硬和功能障礙比較,差異有統(tǒng)計(jì)學(xué)意義(P＜0.05)。兩組治療前后VAS評(píng)分比較,差異有統(tǒng)計(jì)學(xué)意義(P＜0.05);兩組治療后VAS評(píng)分比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P＞0.05)。兩組治療前后 IL-6、TNFα和 TNFsR-Ⅰ比較,差異有統(tǒng)計(jì)學(xué)意義(P＜0.05);對(duì)照組治療前后IL-1β水平比較,差異有統(tǒng)計(jì)學(xué)意義(P＜0.05);治療組治療前后apelin水平比較,差異有統(tǒng)計(jì)學(xué)意義(P＜0.05),兩組治療后apelin水平比較,差異有統(tǒng)計(jì)學(xué)意義(P＜0.05)。結(jié)論 電針治療膝骨關(guān)節(jié)炎療效滿意,可顯著改善患者的臨床癥狀、體征,并可通過(guò)調(diào)控細(xì)胞因子的表達(dá)起到鎮(zhèn)痛、緩解癥狀的作用。

針刺療法;電針;骨關(guān)節(jié)炎,膝關(guān)節(jié);細(xì)胞因子;WOMAC;VAS

膝骨關(guān)節(jié)炎(Knee Osteoarthritis, KOA)是多因素導(dǎo)致的以膝關(guān)節(jié)軟骨破壞為主的慢性退行性骨關(guān)節(jié)疾病,主要表現(xiàn)為疼痛、腫脹及關(guān)節(jié)進(jìn)行性功能活動(dòng)障礙,嚴(yán)重影響患者生活質(zhì)量。膝骨關(guān)節(jié)炎的發(fā)病率和患病率均非常高,世界衛(wèi)生組織估計(jì)全球60歲以上的人口約有 10%會(huì)出現(xiàn)相關(guān)的臨床癥狀,人群中發(fā)生膝骨關(guān)節(jié)炎的概率是45%(其中男性為40%,女性為47%)[1-2],治療該病引起的醫(yī)療花費(fèi)也造成了社會(huì)沉重的經(jīng)濟(jì)負(fù)擔(dān)[3]。目前膝骨關(guān)節(jié)炎的治療仍以控制癥狀為主,以緩解疼痛、改善關(guān)節(jié)功能為治療的主要目標(biāo),藥物治療方面,西醫(yī)主要采用非甾體抗炎藥為主,緩解炎癥和疼痛,但并不能阻止骨關(guān)節(jié)炎的病理進(jìn)程,且長(zhǎng)期使用可損害軟骨并伴隨嚴(yán)重的不良反應(yīng)[4]。近年來(lái),筆者于上海中醫(yī)藥大學(xué)附屬曙光醫(yī)院針灸科采用電針治療膝骨關(guān)節(jié)炎患者 30例,并與單純藥物治療相比較,現(xiàn)報(bào)告如下。

1 臨床資料

1.1 一般資料

60例病例均為2013年1月至2015年12月上海中醫(yī)藥大學(xué)附屬曙光醫(yī)院針灸科收治的膝骨關(guān)節(jié)炎患者,采用隨機(jī)數(shù)字表法分為治療組和對(duì)照組,每組 30例。治療組中男6例,女24例;平均年齡(60±10)歲;平均病程(29.89±29.74)個(gè)月。對(duì)照組中男 7例,女23例;平均年齡(64±6)歲;平均病程(32.74±31.43)個(gè)月。兩組患者性別、年齡和病程等一般情況比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P＞0.05),具有可比性。

1.2 診斷標(biāo)準(zhǔn)

西醫(yī)診斷與分級(jí)標(biāo)準(zhǔn)參照美國(guó)風(fēng)濕病協(xié)會(huì)(American Rheumatism Association,ARA)膝骨關(guān)節(jié)炎的診斷標(biāo)準(zhǔn)[5]以及膝骨關(guān)節(jié)炎 X線病情 Kellgren-Lawrence分級(jí)系統(tǒng)[6]。

1.3 納入標(biāo)準(zhǔn)

①符合上述西醫(yī)診斷標(biāo)準(zhǔn);②年齡 38～80歲;③自愿參加試驗(yàn)并簽署知情同意書(shū)。

1.4 排除標(biāo)準(zhǔn)

①已接受其他有關(guān)治療,可能影響本研究效應(yīng)者;②有明顯膝關(guān)節(jié)內(nèi)外翻畸形或患肢有血管神經(jīng)損傷史者;③妊娠或哺乳期患者。

2 治療方法

2.1 治療組

取陽(yáng)陵泉、梁丘、足三里、內(nèi)膝眼、犢鼻?；颊呷⊙雠P位,采用針管進(jìn)針?lè)?、迎隨瀉法、逆經(jīng)方向斜刺1.2～1.5寸。進(jìn)針后電針連接陽(yáng)陵泉和梁丘穴,刺激參數(shù)為連續(xù)波,頻率 2 Hz,電流 0.5～1.5 mA,時(shí)間30 min。隔日1次,14 d為1個(gè)療程。

2.2 對(duì)照組

予塞來(lái)昔布膠囊(Celecoxib Capsules,商品名西樂(lè)葆,輝瑞制藥有限公司生產(chǎn))口服,每次200 mg,每日1次,14 d為1個(gè)療程。

3 治療效果

3.1 觀察指標(biāo)

3.1.1 WOMAC骨關(guān)節(jié)炎評(píng)分量表

采用國(guó)際公認(rèn)的骨關(guān)節(jié)炎評(píng)價(jià)量表——西安大略麥馬斯特大學(xué)骨性關(guān)節(jié)炎指數(shù)(Western Ontario and McMaster Universities Osteoarthritis Index,WOMAC),對(duì)患者從疼痛、僵硬和關(guān)節(jié)功能3個(gè)方面進(jìn)行評(píng)價(jià),得分越高說(shuō)明患者病情越嚴(yán)重。

3.1.2 視覺(jué)模擬評(píng)分法(visual analogue scale,VAS)

治療前后采用VAS評(píng)分評(píng)價(jià)患者對(duì)疼痛緩解程度的主觀評(píng)價(jià)。

3.1.3 血清相關(guān)細(xì)胞因子測(cè)定

采用酶聯(lián)免疫吸附法(ELISA)檢測(cè)患者治療前后血清中 apelin(北京康肽生物科技公司)、TNFα、TNFsR-Ⅰ、TNFsR-Ⅱ、IL-1β、和IL-6(上海源葉科技有限公司)的含量。

3.2 統(tǒng)計(jì)學(xué)方法

采用SPSS16.0軟件對(duì)數(shù)據(jù)進(jìn)行統(tǒng)計(jì)學(xué)分析。計(jì)量資料以均數(shù)±標(biāo)準(zhǔn)差表示,采用t檢驗(yàn);計(jì)數(shù)資料采用卡方檢驗(yàn)。以P＜0.05為差異有統(tǒng)計(jì)學(xué)意義。

3.3 治療結(jié)果

3.3.1 兩組治療前后WOMAC評(píng)分比較

由表1可見(jiàn),兩組患者治療后WOMAC總評(píng)分、疼痛和功能障礙評(píng)分與同組治療前比較,差異有統(tǒng)計(jì)學(xué)意義(P＜0.05,P＜0.01),說(shuō)明兩種治療方法均能不同程度地改善膝骨關(guān)節(jié)炎的癥狀及嚴(yán)重程度;但僵硬評(píng)分僅治療組治療后與治療前比較,差異具有統(tǒng)計(jì)學(xué)意義(P＜0.01),同時(shí)治療組治療后WOMAC總評(píng)分、僵硬和功能障礙評(píng)分與對(duì)照組比較差異均有具統(tǒng)計(jì)學(xué)意義(P＜0.05),說(shuō)明治療組在改善關(guān)節(jié)功能方面治療效果優(yōu)于對(duì)照組。

表1 兩組治療前后WOMAC評(píng)分比較 (±s,分)

表1 兩組治療前后WOMAC評(píng)分比較 (±s,分)

注:與同組治療前比較1)P＜0.05,2)P＜0.01;與對(duì)照組比較3)P＜0.05

項(xiàng)目 治療組(例數(shù)=30) 對(duì)照組(例數(shù)=30)治療前 治療后 治療前 治療后疼痛 19.07±4.14 13.85±3.022)19.37±10.14 14.17±3.692)僵硬 5.19±1.39 3.30±1.172)3)5.70±2.77 5.57±2.48功能障礙 64.41±12.54 46.67±10.812)3)65.00±32.38 58.67±28.601)總評(píng)分 88.67±16.93 63.82±12.412)3)90.07±43.42 78.41±37.192)

3.3.2 兩組治療前后VAS評(píng)分比較

由表2可見(jiàn),兩組患者治療后VAS評(píng)分與同組治療前比較,差異有統(tǒng)計(jì)學(xué)意義(P＜0.05),但兩組患者治療后VAS評(píng)分比較差異無(wú)有統(tǒng)計(jì)學(xué)意義(P＞0.05),說(shuō)明兩種治療方法均能不同程度地改善膝骨關(guān)節(jié)炎患者對(duì)疼痛的主觀評(píng)價(jià)。

3.3.3 兩組治療前后血清相關(guān)細(xì)胞因子含量比較

由表3可見(jiàn),治療組和對(duì)照組治療后血清IL-6、TNFα、和TNFsR-Ⅰ水平較同組治療前降低(P＜0.05),但 TNFsR-Ⅱ水平無(wú)顯著性改變(P＞0.05)。對(duì)照組治療后血清IL-1β水平低于治療前(P＜0.05)。治療組治療后血清 apelin水平低于治療前(P＜0.05),且治療組低于對(duì)照組(P＜0.05)。

表2 兩組患者治療前后VAS評(píng)分比較 (±s,分)

表2 兩組患者治療前后VAS評(píng)分比較 (±s,分)

注:與同組治療前比較1)P＜0.05

組別 例數(shù) 治療前 治療后治療組 30 4.81±1.04 3.30±1.021)對(duì)照組 30 4.77±1.37 3.41±1.141)

表3 兩組治療前后相關(guān)細(xì)胞因子含量比較 (±s)

表3 兩組治療前后相關(guān)細(xì)胞因子含量比較 (±s)

注:與同組治療前比較1)P＜0.05;與對(duì)照組比較2)P＜0.05

項(xiàng)目 治療組(例數(shù)=30) 對(duì)照組(例數(shù)=30)治療前 治療后 治療前 治療后apelin(ng/mL) 1.16±0.14 0.95±0.091)2)1.15±0.08 1.14±0.06 IL-1β(pg/mL) 26.14±11.88 23.58±13.82 27.31±13.58 21.64±11.521)IL-6(pg/mL) 19.17±7.49 16.92±6.931)18.73±8.03 16.35±6.391)TNFα(pg/mL) 36.81±19.94 32.82±15.551)37.07±20.53 31.77±16.361)TNFsR-Ⅰ(ng/mL) 1.68±0.71 1.52±0.651)1.64±0.84 1.48±0.571)TNFsR-Ⅱ(ng/mL) 3.33±1.41 3.50±1.62 3.41±1.27 3.27±1.57

4 討論

中醫(yī)學(xué)古代文獻(xiàn)中,并無(wú)“膝骨關(guān)節(jié)炎”之說(shuō),根據(jù)其癥狀體征,應(yīng)歸屬于中醫(yī)學(xué)“痹證”范疇。一些研究提示電針對(duì)各種關(guān)節(jié)炎性痛均產(chǎn)生不同程度的鎮(zhèn)痛效應(yīng),同時(shí)還能改善和促進(jìn)關(guān)節(jié)病變區(qū)域功能的恢復(fù)[7-8]。本研究采用的是局部電針刺激的針刺治療方法。所取陽(yáng)陵泉穴為足少陽(yáng)膽經(jīng)之合穴,又因其位于膝下,膝為筋之府,故為筋會(huì)。《銅人腧穴針灸圖經(jīng)》:“治膝伸不得屈,冷痹腳不仁,偏風(fēng)半身不遂,腳冷無(wú)血色?！薄夺樉拇蟪伞?“主膝股內(nèi)外廉不仁,偏風(fēng)半身不遂,腳冷無(wú)血色……”梁丘為足陽(yáng)明胃經(jīng)之郄穴,是經(jīng)脈在四肢部經(jīng)氣深聚的部位,臨床上陽(yáng)經(jīng)郄穴多用于治療急性疼痛,故梁丘可用于治療痛癥[9-12]。《針灸大成》:“主膝腳腰痛,冷痹不仁,跪難屈伸,足寒,大驚,乳腫痛。”因此取此兩穴為主穴進(jìn)行電針刺激。另外還選取了足三里、內(nèi)膝眼、犢鼻進(jìn)行局部針刺。足三里為足陽(yáng)明胃經(jīng)之合穴,又是六腑下合穴之胃下合穴。本穴主治廣泛,為強(qiáng)健身體的要穴,亦可用于治療膝痛等?！鹅`樞·五邪》:“……陰陽(yáng)俱有余,若俱不足,則有寒有熱,皆調(diào)于足三里?！毕パ塾袃?nèi)外兩穴,《太平圣惠方》記載,膝眼“治膝冷,疼痛不已”?！夺樉拇蟪伞分小秳儆窀琛?“兩膝無(wú)端腫如斗,膝眼三里艾當(dāng)施?！惫P者采用以上穴位通過(guò)對(duì)膝關(guān)節(jié)的局部刺激,改善局部的血液循環(huán),促進(jìn)組織代謝,從而達(dá)到減輕疼痛,改善癥狀,促進(jìn)關(guān)節(jié)功能恢復(fù)的作用。從WOMAC評(píng)分結(jié)果說(shuō)明,電針可有效改善患者的膝關(guān)節(jié)疼痛、僵硬和功能障礙。疼痛方面VAS評(píng)分的變化趨勢(shì)與WOMAC疼痛評(píng)分變化趨勢(shì)一致,表明電針治療可有效緩解膝骨關(guān)節(jié)炎患者的疼痛,但并不優(yōu)于西藥。

研究表明,促炎細(xì)胞因子包括TNFα、IL-1β和IL-6等在骨關(guān)節(jié)炎的發(fā)生發(fā)展中發(fā)揮重要作用[13-16]。骨關(guān)節(jié)炎發(fā)生時(shí),關(guān)節(jié)液和滑膜組織中產(chǎn)生大量促炎細(xì)胞因子加速軟骨基質(zhì)降解,從而導(dǎo)致軟骨組織代謝失衡,加劇軟骨的破壞,導(dǎo)致關(guān)節(jié)炎癥的發(fā)生[17]。當(dāng)促炎細(xì)胞因子從受損組織釋放至關(guān)節(jié)腔,它們可調(diào)節(jié)和敏化中樞和外周傷害性感受器,持續(xù)加重疼痛[18]。IL-1β可以加速降解透明軟骨型膠原,并且?guī)椭w維軟骨型膠原的增生,同時(shí)還使蛋白聚糖的分解速度大于合成速度,最直接地介導(dǎo)了軟骨的破壞[19-20]。IL-6是在骨關(guān)節(jié)炎中導(dǎo)致軟骨下骨層病變的關(guān)鍵細(xì)胞因子,能夠激活不成熟的破骨細(xì)胞,刺激破骨細(xì)胞的形成[21-22]。TNFα在骨關(guān)節(jié)炎中的軟骨基質(zhì)降解和骨吸收中發(fā)揮重要作用,它能顯著抑制軟骨細(xì)胞中蛋白多糖、連接蛋白和Ⅱ型膠原的合成[23]。游離的TNFα作用于靶細(xì)胞的受體而發(fā)揮生物活性作用。TNF受體分為兩類(lèi),一類(lèi)為α型TNFR,又稱(chēng)為Ⅱ型TNFR(TNFsR-Ⅱ);另一類(lèi)為β型TNFR,又稱(chēng)Ⅰ型 TNFR(TNFsR-Ⅰ)。在骨關(guān)節(jié)炎中,它們均參與了TNFα介導(dǎo)的病理性信號(hào)通路激活和轉(zhuǎn)導(dǎo)[24-25]。在骨關(guān)節(jié)炎的發(fā)生發(fā)展過(guò)程中,IL-1β、IL-6和 TNFα往往相互協(xié)同加速關(guān)節(jié)損傷和加重疼痛。而apelin是一種脂肪細(xì)胞因子,廣泛分布于中樞神經(jīng)系統(tǒng)和外周組織中,參與多種生理和病理過(guò)程,包括炎癥、疼痛和骨關(guān)節(jié)炎[26-27]。以往的研究提示apelin可能是電針效應(yīng)的一個(gè)潛在效應(yīng)物質(zhì)和靶點(diǎn)[28]。本次研究結(jié)果表明,電針治療可有效減輕膝骨關(guān)節(jié)炎患者血清中apelin、IL-6、TNFα和 TNFsR-Ⅰ的水平,達(dá)到鎮(zhèn)痛、緩解癥狀、改善關(guān)節(jié)功能的作用。

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Clinical Study on Electroacupuncture for Knee Osteoarthritis

JU Zi-yong1,WANG Ying1,CHEN Chang-le2,CUI Hua-shun3,DING Jia-yan1,WANG Ke3. 1.Shanghai University of Traditional Chinese Medicine,Shanghai201203,China; 2.Shanghai Qigong Research Institute,Shanghai200030,China;3.Shuguang Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai201203,China

Objective To observe the clinical efficacy of electroacupuncture (EA) in treating knee osteoarthritis(KOA). Method Sixty KOA patients were randomized into a treatment group and a control group by using random number table, 30 cases each. The control group was intervened by oral administration of Celecoxib capsules, while the treatment group was given EA, 14 d as a treatment course. The changes of relevant cytokines [apelin, tumor necrosis factor (TNF)-α, TNF soluble receptor (TNFsR)-Ⅰ, TNFsR-Ⅱ, interleukin (IL)-1β, and IL-6]in serum of the two groups were observed. Result The intra-group comparisons of the total score, and the scores of pain, stiffness and dysfunction of the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index showed significant differences in both groups (P＜0.05); there were significant between-group differences in comparing the total score,and the scores of pain, stiffness and dysfunction of the WOMAC index after the treatment (P＜0.05). The Visual Analogue Scale (VAS) scores were changed significantly after the intervention in both groups (P＜0.05); there was nosignificant difference in comparing the VAS score between the two groups after the treatment (P＞0.05). The levels of IL-6, TNF-α and TNFsR-Ⅰ were significantly changed after the treatment in both groups (P＜0.05); the level of IL-1β was markedly changed after the intervention in the control group (P＜0.05); there was a significant change in the level of apelin after the intervention in the treatment group (P＜0.05), and there was a significant difference in comparing the level of apelin between the two groups after the treatment (P＜0.05). Conclusion EA can produce a satisfactory efficacy in treating KOA; it can significantly improve the symptoms and signs, and mitigate pain and symptoms through regulating the expressions of cytokines.

Acupuncture therapy; Electroacupuncture; Osteoarthritis, Knee; Cytokine; WOMAC; VAS

R246.2

A

2017-04-05

10.13460/j.issn.1005-0957.2017.09.1111

1005-0957(2017)09-1111-05

國(guó)家自然科學(xué)基金(81202767);上海市自然科學(xué)基金(15ZR1441300);上海市衛(wèi)生局中醫(yī)藥科研基金項(xiàng)目(2012QL016A;2014JP030A);國(guó)家體育總局氣功中心科研課題(QG2016045);上海市中醫(yī)藥事業(yè)發(fā)展三年行動(dòng)計(jì)劃項(xiàng)目(ZY3-CCCX-2-1003)

具紫勇(1979—),男,副教授,博士,Email:juziyong@hotmail.com

王珂(1980—),男,副研究員,博士,Email:wangke8430@163.com