电温针对膝骨关节炎患者血清细胞因子与生存质量的影响
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摘要
研究背景
膝关节骨性关节炎(Knee osteoarthritis,简称KOA),属于骨性关节炎(Osteoarthritis, OA)的一种,本病为50岁以上老年人中最常见的骨骼肌肉系统疾病。其基本病理特征为关节软骨组织发生进行性退变、消失,关节边缘骨赘形成和软骨下骨质反应性改变,病变的过程涉及整个关节,包括软骨下骨、韧带、关节、滑膜及关节周围肌肉,病变结果通常最终导致关节功能障碍甚至残疾,是引起老年人疼痛和伤残的主要原因之一。近年来随着世界老龄化人口的增加,OA的发病率也呈逐年上升趋势,医学界至今对其发病机制并不完全清楚,有关OA发病机理的研究主要集中在炎性细胞因子、细胞凋亡及生长因子等方面。研究发现,IL-1、TNF-α、NO、MMPs等存在于骨、软骨组织及关节滑膜中,可通过自分泌或旁分泌方式对骨和软骨的形成与修复起局部调节作用,从而调控“骨吸收一骨形成”偶联的动态平衡,维持关节软骨的正常形态和功能,若其活性发生改变,则将导致关节软骨基质成分的丢失和进行性破坏。目前针对本病的各项保守治疗措施均存在一定缺陷,或者具有药物毒副作用,或者无法推广应用,而后期手术治疗效果亦不肯定,且经济负担较重,严重影响患者的身体健康和生活质量；相对来说,作为传统医疗手段之一的针灸疗法治疗本病不仅具有较高的临床好转率,且毒副作用少、简便易行,被广泛应用于我国临床与科研中。
目的
本课题在既往研究基础上,观察电针结合温针灸疗法(简称电温针)治疗膝骨性关节炎的临床疗效,并比较三组不同治疗方式的效果,以及对KOA患者生存质量的影响；同时,检测患者治疗前后血清白介素-1(IL-1)、肿瘤坏死因子-α(TNF-α)的含量,来进一步探讨针灸治疗KOA的可能作用机理。期望通过本次研究,能为日后临床治疗该病提供一项安全有效的措施,并进而为提高患者生存质量贡献一份心力。
方法
选择广州中医药大学第一附属医院2010年5月～2010年12月的针灸科和骨科门诊病人共90名为研究对象,按随机化原则,将符合纳入标准的90例膝骨性关节炎患者分为治疗组(电针结合温针灸组)30例、对照Ⅰ组(电针组)30例、对照Ⅱ组(西乐葆组)30例。各组具体研究方法分别为：
一、治疗组：采用电针加温针灸治疗,配合循经取穴与辨证取穴。主穴：取内、外膝眼、鹤顶、膝阳关、曲泉、阿是穴。配穴：肾虚髓亏型,配绝骨、太溪、阳陵泉；阳虚寒凝型,配梁丘、足三里、阴陵泉；瘀血阻滞型,配血海。操作方法：穴位常规消毒后,取1.5寸毫针进行治疗,实证用泻法,虚证用补法。针刺后加电针仪选用疏密波中的密波,电流强度以病人舒适为宜,同时在主穴针柄上插上一段长约2cm的艾柱,点燃行温灸治疗,艾柱燃完后除去灰烬,连灸2壮,留针30分钟,每两日一次,一周3次,连续治疗4周。
二、对照Ⅰ组：采用电针治疗,取穴、针刺方法与治疗时间均同治疗组。
三、对照Ⅱ组：给予口服塞来昔布(商品名西乐葆胶囊)0.2g Qd治疗,若患者服药期间出现胃肠道不适反应,可视具体情况给予胃肠道保护剂奥美拉唑20mg Qd治疗,观察时间亦为4周。
三组治疗前后均从以下几个方面进行临床观察：(1)SF-36生存质量调查问卷(中文版),该量表广泛使用于临床,有较好的信度、效度和代表性,作为生存质量的主要结局指标。其中共有躯体健康(PF)、体角色功能(RP)、躯体疼痛(BP)、总体健康(GH)、活力(VT)、社会功能(SF)、情绪角色功能(RE)、心理健康(MH)等8个维度,每个维度包含若干问题,共35个项目；另一项目为健康变化自评(HT),作单纯分析；(2)膝骨关节炎中医生存质量量化评分表,该表主要为参考国际生存质量评价标准而改良制定的积分表,且所选项目较贴近我国患者的实际生活情况,故作为次要结局指标。其内容大致分为生理功能(形)、心理状况(情)、社会功能(神)、健康地自我认识(总体主观健康)等四个部分。(3)外周血中IL-1、TNF-α水平,按实验室检测指标规定,分别抽取静脉血并保存,治疗前后对标本中IL-1、TNF-α指标进行检测。同时另设正常健康人(40岁以上)15例,测其血清IL-1、TNF-α值作为健康对照组。(4)安全性检测,治疗前后检查血、尿常规、肝肾功能、心电图等,并于治疗期间记录不良反应观察表,疗程结束后填写安全性评价表。三组患者治疗前及治疗4周后进行电话随访、问卷评分。将全部数据输入SPSS13.0统计软件,对数据资料进行统计学处理及分析,得出结论。
结果
在实验过程中治疗组有2例失访；对照Ⅰ组有3例失访；对照Ⅱ组有2例失访,另有2例则因出现不良反应而退出试验。总脱落例数共9例,故实验完成后实际共有患者81例,其中治疗组28例、对照Ⅰ组27例,对照Ⅱ组26例,具体治疗结果如下：
一、治疗前三组患者在性别、年龄、病程、发病部位、X线分级与中医证型等各项基本资料间差异无统计学意义(P>0.05),提示彼此间具有较好的可比性。
二、治疗前后三组生存质量比较
(1)SF-36生存质量调查问卷：
治疗前三组在8个维度上均无明显差异(P>0.05),说明三组间具有可比性。统计结果显示,运用电针结合温针灸疗法的治疗组在改善患者生存质量,如生命活力、社会功能、心理健康及总体健康等方面的作用,其疗效更优于采用电针与口服西乐葆的方式(P<0.01)；但三组在改善躯体健康、躯体疼痛两方面,其各组间的程度并无明显差异(P>0.05),说明三组在控制膝骨关节炎患者关节疼痛与改善临床体征方面的疗效相当。
(2)膝骨关节炎中医生存质量量化评分表：
治疗前三组在生理功能、心理状态、社会功能、总体主观健康与综合积分上均无明显差异(P>0.05),说明三组间具有可比性。统计结果显示,治疗组在改善患者中医生存质量方面疗效更优于其他各对照组(P<0.01)；此外,数据也提示采用电针方式,对于改善膝骨关节炎患者的生理功能与心理状态,确实可以起到一定的疗效。
三、治疗前后三组体征指标比较
治疗前三组患者的体征指标积分均无显著性差异(P>0.05),说明三组治疗前病情具有可比性。统计结果显示,治疗后治疗组在直腿抬高时间与步行15米时间的改善上均明显优于其他各对照组(P<0.01)。
四、治疗前后三组血清IL-1、TNF-α比较
治疗前三组KOA患者血清IL-1和TNF-α水平均明显高于正常人,与正常组相比有显著性差异(P<0.01)；而三组治疗前IL-1、TNF-α含量均无显著性差异(P>0.05),说明三组患者治疗前的细胞因子水平具有可比性。统计结果显示,治疗组治疗前后血清IL-1和TNF-α含量明显降低,具有显著性差异(P<0.01),对照Ⅰ组治疗后也有差异(P<0.05),而对照Ⅱ组治疗后则无统计学意义(P>0.05)；三组间比较,治疗组与对照Ⅰ组、对照Ⅱ组相比均具有显著性差异(P<0.01),而两对照组间疗效则无差异(P>0.05)。其数据说明电针结合温针灸组在调控血清细胞因子水平方面,疗效明显优于各对照组。
五、治疗后三组疗效比较
治疗后治疗组总有效率为92.9%,对照Ⅰ组总有效率为70.4%,对照Ⅱ组总有效率为65.4%,提示治疗组总有效率明显高于各对照组,三组间差异有统计学意义(P<0.05)。统计结果说明运用电针结合温针灸治疗膝骨性关节炎患者,其疗效明显优于采用电针和口服西药的治疗方法。
六、治疗后三组不良反应比较
整个研究过程中,电针结合温针灸组和电针组无1例出现不良反应,而西乐葆组则有1例患者出现头痛,5例出现胃肠道的不适症状。三组患者经4周治疗后,均未发现肝肾功能损害、血象抑制及消化道出血的症状和体征。
结论
临床观察证实电针可加强针感、促进气血运行、消除炎症水肿,有较强的中枢性镇痛作用,而温针灸所产生的热效应能促进血液循环,改善局部组织代谢的效果。因此将两种疗法结合运用于膝骨关节炎,确实能起到行气活血、温经散寒、消肿止痛、改善关节功能的作用。本研究结果表明,采用电针结合温针灸治疗KOA,不仅能缓解患者的生理不适,对其情绪、活力、日常生活能力等生存质量的改善更为显著,且未发现有明显的临床毒副作用；此外,根据治疗后患者外周血中IL-1、TNF-α含量降低的提示,可推测针灸治疗KOA的机理可能是与其通过下调过高的IL-1、TNF-α水平,从而延缓骨关节炎发展,减少关节骨赘形成有关。
Background
Knee osteoarthritis(KOA) is one of osteoarthritis(OA). It is the most common seen musculoskeletal system disease among seniors above age 50. Its feature symptoms is occurrence or disappearance of progressive articular cartilage degeneration joint edge of the osteophyte formation and subchondral bone reactive changes, disease process involves the entire joint, including subchondral bone, ligaments, joints, and joint synovium the surrounding muscles. The results are usually eventually lead to joint dysfunction or disability. These are the main cause to senior pain and handicap. In recent years, with the world increasing aging population, the incidence of OA increased year by year. However, medical field has not exactly found its pathogenesis yet. Recently, the OA pathogenesis studies have focused on inflammatory cytokines, apoptosis and growth factor and so on. The study found that IL-1, TNF-α, NO, MMPs such as exists in the bone, cartilage and synovial membrane. In manner of autocrine or paracrine they play a part in bone and cartilage formation and repair in order to regulate the coupled dynamic balance of "bone resorption-bone formation" and maintain normal articular cartilage morphology and function. If its activity is changed, it will result in the loss of articular cartilage matrix components and progressive damage. At present the conservative treatment of this disease has some defects, or medication side effects, or has no means of popularization. And it also has uncertain post-operative treatment, heavy economic burden, seriously affect of health and quality of life; In contrast, as a traditional means of medical treatment of the disease acupuncture not only has a high rate of clinical improvement and fewer side effects, convenient, is also widely used in clinical and scientific research in China.
Objective
In view of this, based on the previous study this subject aim to observe of electro acupuncture combined with warm acupuncture treatment of KOA clinical efficacy and to compare three different treatment effects, as well as quality of life of KOA patients; meanwhile, we detect serum levels of interleukin-1(IL-1), tumor necrosis factor-α(TNF-α) of patients, in order to further explore the possible role of acupuncture mechanism of KOA in expectation of providing a safe and effective measures in clinical treatment, and contributing to improve the quality of life of patients through this study in the future.
Method
We selected 90 outpatients of acupuncture and orthopedic clinic of the Guangzhou University of Traditional Chinese Medicine, First Affiliated Hospital of May 2010-2010 in December. According to the principle of randomization, the 90 patients met the inclusion criteria of KOA were divided into treatment group were 30 cases (electropuncture combined with warm needling method group)、30 patients in the control groupⅠ(electropuncture group)、30 cases were the control groupⅡ(Celebrex group). Specific research methods of each group are:
1.Treatment groups:To adopt acupuncture treatment with electropuncture combined with warm needling method, according to the corresponding channel acupoints selection and differentiation of symptoms acupoints selection. The main point:taking the inner and outer Xiyan、EX-LE2、GB33、LR8、Ashi points. Matching acupoints:Loss of kidney marrow type, with GB39、KI3、GB34; Yang deficiency and cold accumulation type, with ST34、ST36、SP9; Blood stasis type, with SP10. Operation:After routine disinfection of the acupoints, we take 1.5-inch needles for treatment, adopting excess syndrome with supplementation, deficiency syndrome with draining. The wave of condensation and rarefaction of the electronic acupunctoscope was selceted after the operation of acupuncture. The amperage was fit for the comfortable feeling of patients. At the same time,2cm long moxa roll was plugged into the needle handle of the main points. Then we lighted the moxa roll till it w as burned out then we rem(?)ove the ash after burned moxa. Two consistent moxa-cones should be used and period of retaining the needles was 30minutes.
2. The control group I:We adopted electropuncture treatment. Acupoints selection and needling methods and time of treatment were as same as treatment group.
3. Control groupⅡ:The patients were given oral celecoxib (brand name Celebrex capsules)0.2g Qd therapy.In case of discomfort of the gastrointestinal tract, patients should be given Omeprazole the protectant of gastrointestinal tract 20mg Qd depending on the particular circumstances. The observation time is also 4 weeks.
Three groups before and after treatments should be observed with the following aspects:(1) SF-36 quality of life questionnaire (Chinese version), which are widely used in clinical scale and it has good reliability, validity and representativeness as the main outcome measures quality of life. Among them, physical health (PF), physical role function (RP), bodily pain (BP), general health (GH), vitality (VT), social function(SF), emotional role function ing (RE), mental health (MH) other 8 dimensions, each dimension contains a number of issues, a total of 35 projects; another item changes for health self-assessment (HT), for the simple analysis; (2) KOA quantified Chinese quality of life score table, which mainly refer to international standards of quality of life and make a improvement.The selected items are closer to the actual living conditions of patients, so we take them as secondary outcomes. Its content can be divided into physiological function (shape), psychological (feelings), social function (spirit), and healthy self-awareness (general subjective health) and other four parts. (3) According to the provisions of laboratory, IL-1、TNF-αlevels of peripheral blood of samples are tested before and after treatment. At the same time take 15 healthy people (above 40 years) as the healthy control group then have them serum IL-1、TNF-αtested. (4) Safety testing. Inspection of blood、urine、liver and kidney function、ECG, etc should be taken before and after treatment. During the treatment adverse reactions must be recorded. After completing course of treatment the patients should fill safety evaluation form. Additionally three groups of patients before treatment and after 4 weeks are asked for treatment telephone follow-up and the questionnaire score. We enter all data into SPSS13.0 the statistical software for data processing and analysis of statistical data and finally draw conclusions.
Result
During the experiment, there was 2 patients lost in the treatment group; 3 were lost in the control groupⅠto follow; 2 cases were lost in the control groupⅡ. There were 2 patients withdrew due to adverse reaction test. The total lost cases were 9, so the there were 81 cases actually after completion of the experiment, which of 28 cases in treatment group and 27 cases in control groupⅠ,26 cases in the control groupⅡ. Specific treatment was as follows:
1. There was no significantly difference among the three groups of patients in aspect of gender, age, disease duration, disease location, X ray classification and syndromes, and other basic information (P>0.05), suggesting a better comparability among them.
2. Comparision of quality of life before and after treatment three groups.
(1) SF-36 quality of life questionnaire:
The three groups in the 8 dimensions had no significant differences (P > 0.05), It means that is comparability among the three groups. The results showed that the treatment group which was adopted the method of electropuncture combined with warm acupuncture have an advantage over the simple acupuncture and oral use of Celebrex (P<0.01) in improving the quality of life of patients, such as vitality, social functioning, mental health and overall health and so on. However there was no significant difference between the three groups in improving physical health and pain (P>0.05). It indicated that both three groups of patients with knee osteoarthritis have similar effect on the control joint pain and improve the efficacy of clinical signs.
(2) KOA quantified Chinese quality of life score table:
There were no significant differences in physiological function psychological condition、social function general and comprehensive integration of subjective health of three groups before the treatment (P> 0.05). There was comparability among the three groups. The results showed that the treatment group in improving the quality of life of patients is more offective than other control groups (P<0.01); In addition, the data also suggest using electropuncture for osteoarthritis of the knee to improve physical function in patients with state of mind, can indeed play a certain effect.
3. Comparasion of physical sign indicators of three groups before and after treatment.
The physical sign indicators of three groups had no significant differences (P>0.05) before treatment. It means that is comparability among the three groups. The results showed that, both time and walk in the straight leg raising to improve on the 15-meter time of the treatment group was superior to the other control groups (P<0.01).
4. Comparasion of serum IL-1, TNF-αof three groups before and after treatment.
The KOA IL-1 and TNF-αof three groups before treatment were significantly higher than normal people, which meant significant difference compared with the normal group (P<0.01); However, IL-1、TNF-αlevels have no significantly differences among the three groups before treatment (P>0.05), which indicated that three groups of patients before treatment were comparable in levels of cytokines. The results presented that the serum IL-1 and TNF-αdecreased significantly, with significant differences (P<0.01). The control groupⅠafter treatment also has differences (P<0.05), while the control groupⅡafter treatment has no statistical significance (P>0.05); Comparison among the three groups, the treatment group and control groupⅠ、Ⅱgroup control had significant differences (P<0.01), while the two control groups did not differ between the effect (P>0.05). The data of electropuncture combined with warm needling method group in terms of serum cytokine levels, significantly superior to the control group.
5. Comparaion of curative effect of the three groups after treatment.
After treatment, the total effective rate of treatment group was 92.9%, total effective rate of the control groupⅠwas 70.4%, total effective rate of the control groupⅡwas 65.4%, indicating that the effective rate of treatment group was significantly higher than the control group. Statistical differences among the three groups had significance (P<0.05). Statistical results indicate that the use of electropuncture combined with warm needling method treatment of KOA patients, significantly better than using electropuncture treatment and oral medicine.
6. Comparasion of adverse reactions of the three groups after treatment.
Throughout the study, the electropuncture combined with warm needling method group and the electropuncture group had no case of adverse reactions, while 1 patient had headache and 5 patients of the Celebrex group had gastrointestinal symptoms. Three groups of patients, were not found liver and kidney dysfunction, inhibition of blood and signs and symptoms of gastrointestinal bleeding after 4 weeks of treatment.
Conclusion
Clinical observation confirmed that acupuncture can enhance a sense of EA to promote the blood running, eliminate inflammatory edema, has a strong central analgesic effect; The temperature of the thermal effects produced by warm needling method, can promote blood circulation, improve the effectiveness of local tissue metabolism. Therefore, the combination of the two treatments used in KOA can indeed play a role in promoting qi and blood circulation and warming channel and expelling cold, reduce swelling and alleviate pain, improve joint function. The results show that electropuncture combined with warm needling method in treating KOA, not only can ease the physical discomfort of patients, the quality of life such as their emotions, vitality, activity of daily life is also improved even more significantly. Moreover obvious side effects had reported. In addition, according to the tips of decreasing IL-1、TNF-αof patients under treatment, we suggest that the mechanism of acupuncture treatment of KOA may be in relation to reduce excess IL-1、TNF-αlevels. Therefore it can delay osteoarthritis development, and reduce joint osteophyte formation.
膝关节骨性关节炎(Knee osteoarthritis,简称KOA),属于骨性关节炎(Osteoarthritis, OA)的一种,本病为50岁以上老年人中最常见的骨骼肌肉系统疾病。其基本病理特征为关节软骨组织发生进行性退变、消失,关节边缘骨赘形成和软骨下骨质反应性改变,病变的过程涉及整个关节,包括软骨下骨、韧带、关节、滑膜及关节周围肌肉,病变结果通常最终导致关节功能障碍甚至残疾,是引起老年人疼痛和伤残的主要原因之一。近年来随着世界老龄化人口的增加,OA的发病率也呈逐年上升趋势,医学界至今对其发病机制并不完全清楚,有关OA发病机理的研究主要集中在炎性细胞因子、细胞凋亡及生长因子等方面。研究发现,IL-1、TNF-α、NO、MMPs等存在于骨、软骨组织及关节滑膜中,可通过自分泌或旁分泌方式对骨和软骨的形成与修复起局部调节作用,从而调控“骨吸收一骨形成”偶联的动态平衡,维持关节软骨的正常形态和功能,若其活性发生改变,则将导致关节软骨基质成分的丢失和进行性破坏。目前针对本病的各项保守治疗措施均存在一定缺陷,或者具有药物毒副作用,或者无法推广应用,而后期手术治疗效果亦不肯定,且经济负担较重,严重影响患者的身体健康和生活质量；相对来说,作为传统医疗手段之一的针灸疗法治疗本病不仅具有较高的临床好转率,且毒副作用少、简便易行,被广泛应用于我国临床与科研中。
目的
本课题在既往研究基础上,观察电针结合温针灸疗法(简称电温针)治疗膝骨性关节炎的临床疗效,并比较三组不同治疗方式的效果,以及对KOA患者生存质量的影响；同时,检测患者治疗前后血清白介素-1(IL-1)、肿瘤坏死因子-α(TNF-α)的含量,来进一步探讨针灸治疗KOA的可能作用机理。期望通过本次研究,能为日后临床治疗该病提供一项安全有效的措施,并进而为提高患者生存质量贡献一份心力。
方法
选择广州中医药大学第一附属医院2010年5月～2010年12月的针灸科和骨科门诊病人共90名为研究对象,按随机化原则,将符合纳入标准的90例膝骨性关节炎患者分为治疗组(电针结合温针灸组)30例、对照Ⅰ组(电针组)30例、对照Ⅱ组(西乐葆组)30例。各组具体研究方法分别为：
一、治疗组：采用电针加温针灸治疗,配合循经取穴与辨证取穴。主穴：取内、外膝眼、鹤顶、膝阳关、曲泉、阿是穴。配穴：肾虚髓亏型,配绝骨、太溪、阳陵泉；阳虚寒凝型,配梁丘、足三里、阴陵泉；瘀血阻滞型,配血海。操作方法：穴位常规消毒后,取1.5寸毫针进行治疗,实证用泻法,虚证用补法。针刺后加电针仪选用疏密波中的密波,电流强度以病人舒适为宜,同时在主穴针柄上插上一段长约2cm的艾柱,点燃行温灸治疗,艾柱燃完后除去灰烬,连灸2壮,留针30分钟,每两日一次,一周3次,连续治疗4周。
二、对照Ⅰ组：采用电针治疗,取穴、针刺方法与治疗时间均同治疗组。
三、对照Ⅱ组：给予口服塞来昔布(商品名西乐葆胶囊)0.2g Qd治疗,若患者服药期间出现胃肠道不适反应,可视具体情况给予胃肠道保护剂奥美拉唑20mg Qd治疗,观察时间亦为4周。
三组治疗前后均从以下几个方面进行临床观察：(1)SF-36生存质量调查问卷(中文版),该量表广泛使用于临床,有较好的信度、效度和代表性,作为生存质量的主要结局指标。其中共有躯体健康(PF)、体角色功能(RP)、躯体疼痛(BP)、总体健康(GH)、活力(VT)、社会功能(SF)、情绪角色功能(RE)、心理健康(MH)等8个维度,每个维度包含若干问题,共35个项目；另一项目为健康变化自评(HT),作单纯分析；(2)膝骨关节炎中医生存质量量化评分表,该表主要为参考国际生存质量评价标准而改良制定的积分表,且所选项目较贴近我国患者的实际生活情况,故作为次要结局指标。其内容大致分为生理功能(形)、心理状况(情)、社会功能(神)、健康地自我认识(总体主观健康)等四个部分。(3)外周血中IL-1、TNF-α水平,按实验室检测指标规定,分别抽取静脉血并保存,治疗前后对标本中IL-1、TNF-α指标进行检测。同时另设正常健康人(40岁以上)15例,测其血清IL-1、TNF-α值作为健康对照组。(4)安全性检测,治疗前后检查血、尿常规、肝肾功能、心电图等,并于治疗期间记录不良反应观察表,疗程结束后填写安全性评价表。三组患者治疗前及治疗4周后进行电话随访、问卷评分。将全部数据输入SPSS13.0统计软件,对数据资料进行统计学处理及分析,得出结论。
结果
在实验过程中治疗组有2例失访；对照Ⅰ组有3例失访；对照Ⅱ组有2例失访,另有2例则因出现不良反应而退出试验。总脱落例数共9例,故实验完成后实际共有患者81例,其中治疗组28例、对照Ⅰ组27例,对照Ⅱ组26例,具体治疗结果如下：
一、治疗前三组患者在性别、年龄、病程、发病部位、X线分级与中医证型等各项基本资料间差异无统计学意义(P>0.05),提示彼此间具有较好的可比性。
二、治疗前后三组生存质量比较
(1)SF-36生存质量调查问卷：
治疗前三组在8个维度上均无明显差异(P>0.05),说明三组间具有可比性。统计结果显示,运用电针结合温针灸疗法的治疗组在改善患者生存质量,如生命活力、社会功能、心理健康及总体健康等方面的作用,其疗效更优于采用电针与口服西乐葆的方式(P<0.01)；但三组在改善躯体健康、躯体疼痛两方面,其各组间的程度并无明显差异(P>0.05),说明三组在控制膝骨关节炎患者关节疼痛与改善临床体征方面的疗效相当。
(2)膝骨关节炎中医生存质量量化评分表：
治疗前三组在生理功能、心理状态、社会功能、总体主观健康与综合积分上均无明显差异(P>0.05),说明三组间具有可比性。统计结果显示,治疗组在改善患者中医生存质量方面疗效更优于其他各对照组(P<0.01)；此外,数据也提示采用电针方式,对于改善膝骨关节炎患者的生理功能与心理状态,确实可以起到一定的疗效。
三、治疗前后三组体征指标比较
治疗前三组患者的体征指标积分均无显著性差异(P>0.05),说明三组治疗前病情具有可比性。统计结果显示,治疗后治疗组在直腿抬高时间与步行15米时间的改善上均明显优于其他各对照组(P<0.01)。
四、治疗前后三组血清IL-1、TNF-α比较
治疗前三组KOA患者血清IL-1和TNF-α水平均明显高于正常人,与正常组相比有显著性差异(P<0.01)；而三组治疗前IL-1、TNF-α含量均无显著性差异(P>0.05),说明三组患者治疗前的细胞因子水平具有可比性。统计结果显示,治疗组治疗前后血清IL-1和TNF-α含量明显降低,具有显著性差异(P<0.01),对照Ⅰ组治疗后也有差异(P<0.05),而对照Ⅱ组治疗后则无统计学意义(P>0.05)；三组间比较,治疗组与对照Ⅰ组、对照Ⅱ组相比均具有显著性差异(P<0.01),而两对照组间疗效则无差异(P>0.05)。其数据说明电针结合温针灸组在调控血清细胞因子水平方面,疗效明显优于各对照组。
五、治疗后三组疗效比较
治疗后治疗组总有效率为92.9%,对照Ⅰ组总有效率为70.4%,对照Ⅱ组总有效率为65.4%,提示治疗组总有效率明显高于各对照组,三组间差异有统计学意义(P<0.05)。统计结果说明运用电针结合温针灸治疗膝骨性关节炎患者,其疗效明显优于采用电针和口服西药的治疗方法。
六、治疗后三组不良反应比较
整个研究过程中,电针结合温针灸组和电针组无1例出现不良反应,而西乐葆组则有1例患者出现头痛,5例出现胃肠道的不适症状。三组患者经4周治疗后,均未发现肝肾功能损害、血象抑制及消化道出血的症状和体征。
结论
临床观察证实电针可加强针感、促进气血运行、消除炎症水肿,有较强的中枢性镇痛作用,而温针灸所产生的热效应能促进血液循环,改善局部组织代谢的效果。因此将两种疗法结合运用于膝骨关节炎,确实能起到行气活血、温经散寒、消肿止痛、改善关节功能的作用。本研究结果表明,采用电针结合温针灸治疗KOA,不仅能缓解患者的生理不适,对其情绪、活力、日常生活能力等生存质量的改善更为显著,且未发现有明显的临床毒副作用；此外,根据治疗后患者外周血中IL-1、TNF-α含量降低的提示,可推测针灸治疗KOA的机理可能是与其通过下调过高的IL-1、TNF-α水平,从而延缓骨关节炎发展,减少关节骨赘形成有关。
Background
Knee osteoarthritis(KOA) is one of osteoarthritis(OA). It is the most common seen musculoskeletal system disease among seniors above age 50. Its feature symptoms is occurrence or disappearance of progressive articular cartilage degeneration joint edge of the osteophyte formation and subchondral bone reactive changes, disease process involves the entire joint, including subchondral bone, ligaments, joints, and joint synovium the surrounding muscles. The results are usually eventually lead to joint dysfunction or disability. These are the main cause to senior pain and handicap. In recent years, with the world increasing aging population, the incidence of OA increased year by year. However, medical field has not exactly found its pathogenesis yet. Recently, the OA pathogenesis studies have focused on inflammatory cytokines, apoptosis and growth factor and so on. The study found that IL-1, TNF-α, NO, MMPs such as exists in the bone, cartilage and synovial membrane. In manner of autocrine or paracrine they play a part in bone and cartilage formation and repair in order to regulate the coupled dynamic balance of "bone resorption-bone formation" and maintain normal articular cartilage morphology and function. If its activity is changed, it will result in the loss of articular cartilage matrix components and progressive damage. At present the conservative treatment of this disease has some defects, or medication side effects, or has no means of popularization. And it also has uncertain post-operative treatment, heavy economic burden, seriously affect of health and quality of life; In contrast, as a traditional means of medical treatment of the disease acupuncture not only has a high rate of clinical improvement and fewer side effects, convenient, is also widely used in clinical and scientific research in China.
Objective
In view of this, based on the previous study this subject aim to observe of electro acupuncture combined with warm acupuncture treatment of KOA clinical efficacy and to compare three different treatment effects, as well as quality of life of KOA patients; meanwhile, we detect serum levels of interleukin-1(IL-1), tumor necrosis factor-α(TNF-α) of patients, in order to further explore the possible role of acupuncture mechanism of KOA in expectation of providing a safe and effective measures in clinical treatment, and contributing to improve the quality of life of patients through this study in the future.
Method
We selected 90 outpatients of acupuncture and orthopedic clinic of the Guangzhou University of Traditional Chinese Medicine, First Affiliated Hospital of May 2010-2010 in December. According to the principle of randomization, the 90 patients met the inclusion criteria of KOA were divided into treatment group were 30 cases (electropuncture combined with warm needling method group)、30 patients in the control groupⅠ(electropuncture group)、30 cases were the control groupⅡ(Celebrex group). Specific research methods of each group are:
1.Treatment groups:To adopt acupuncture treatment with electropuncture combined with warm needling method, according to the corresponding channel acupoints selection and differentiation of symptoms acupoints selection. The main point:taking the inner and outer Xiyan、EX-LE2、GB33、LR8、Ashi points. Matching acupoints:Loss of kidney marrow type, with GB39、KI3、GB34; Yang deficiency and cold accumulation type, with ST34、ST36、SP9; Blood stasis type, with SP10. Operation:After routine disinfection of the acupoints, we take 1.5-inch needles for treatment, adopting excess syndrome with supplementation, deficiency syndrome with draining. The wave of condensation and rarefaction of the electronic acupunctoscope was selceted after the operation of acupuncture. The amperage was fit for the comfortable feeling of patients. At the same time,2cm long moxa roll was plugged into the needle handle of the main points. Then we lighted the moxa roll till it w as burned out then we rem(?)ove the ash after burned moxa. Two consistent moxa-cones should be used and period of retaining the needles was 30minutes.
2. The control group I:We adopted electropuncture treatment. Acupoints selection and needling methods and time of treatment were as same as treatment group.
3. Control groupⅡ:The patients were given oral celecoxib (brand name Celebrex capsules)0.2g Qd therapy.In case of discomfort of the gastrointestinal tract, patients should be given Omeprazole the protectant of gastrointestinal tract 20mg Qd depending on the particular circumstances. The observation time is also 4 weeks.
Three groups before and after treatments should be observed with the following aspects:(1) SF-36 quality of life questionnaire (Chinese version), which are widely used in clinical scale and it has good reliability, validity and representativeness as the main outcome measures quality of life. Among them, physical health (PF), physical role function (RP), bodily pain (BP), general health (GH), vitality (VT), social function(SF), emotional role function ing (RE), mental health (MH) other 8 dimensions, each dimension contains a number of issues, a total of 35 projects; another item changes for health self-assessment (HT), for the simple analysis; (2) KOA quantified Chinese quality of life score table, which mainly refer to international standards of quality of life and make a improvement.The selected items are closer to the actual living conditions of patients, so we take them as secondary outcomes. Its content can be divided into physiological function (shape), psychological (feelings), social function (spirit), and healthy self-awareness (general subjective health) and other four parts. (3) According to the provisions of laboratory, IL-1、TNF-αlevels of peripheral blood of samples are tested before and after treatment. At the same time take 15 healthy people (above 40 years) as the healthy control group then have them serum IL-1、TNF-αtested. (4) Safety testing. Inspection of blood、urine、liver and kidney function、ECG, etc should be taken before and after treatment. During the treatment adverse reactions must be recorded. After completing course of treatment the patients should fill safety evaluation form. Additionally three groups of patients before treatment and after 4 weeks are asked for treatment telephone follow-up and the questionnaire score. We enter all data into SPSS13.0 the statistical software for data processing and analysis of statistical data and finally draw conclusions.
Result
During the experiment, there was 2 patients lost in the treatment group; 3 were lost in the control groupⅠto follow; 2 cases were lost in the control groupⅡ. There were 2 patients withdrew due to adverse reaction test. The total lost cases were 9, so the there were 81 cases actually after completion of the experiment, which of 28 cases in treatment group and 27 cases in control groupⅠ,26 cases in the control groupⅡ. Specific treatment was as follows:
1. There was no significantly difference among the three groups of patients in aspect of gender, age, disease duration, disease location, X ray classification and syndromes, and other basic information (P>0.05), suggesting a better comparability among them.
2. Comparision of quality of life before and after treatment three groups.
(1) SF-36 quality of life questionnaire:
The three groups in the 8 dimensions had no significant differences (P > 0.05), It means that is comparability among the three groups. The results showed that the treatment group which was adopted the method of electropuncture combined with warm acupuncture have an advantage over the simple acupuncture and oral use of Celebrex (P<0.01) in improving the quality of life of patients, such as vitality, social functioning, mental health and overall health and so on. However there was no significant difference between the three groups in improving physical health and pain (P>0.05). It indicated that both three groups of patients with knee osteoarthritis have similar effect on the control joint pain and improve the efficacy of clinical signs.
(2) KOA quantified Chinese quality of life score table:
There were no significant differences in physiological function psychological condition、social function general and comprehensive integration of subjective health of three groups before the treatment (P> 0.05). There was comparability among the three groups. The results showed that the treatment group in improving the quality of life of patients is more offective than other control groups (P<0.01); In addition, the data also suggest using electropuncture for osteoarthritis of the knee to improve physical function in patients with state of mind, can indeed play a certain effect.
3. Comparasion of physical sign indicators of three groups before and after treatment.
The physical sign indicators of three groups had no significant differences (P>0.05) before treatment. It means that is comparability among the three groups. The results showed that, both time and walk in the straight leg raising to improve on the 15-meter time of the treatment group was superior to the other control groups (P<0.01).
4. Comparasion of serum IL-1, TNF-αof three groups before and after treatment.
The KOA IL-1 and TNF-αof three groups before treatment were significantly higher than normal people, which meant significant difference compared with the normal group (P<0.01); However, IL-1、TNF-αlevels have no significantly differences among the three groups before treatment (P>0.05), which indicated that three groups of patients before treatment were comparable in levels of cytokines. The results presented that the serum IL-1 and TNF-αdecreased significantly, with significant differences (P<0.01). The control groupⅠafter treatment also has differences (P<0.05), while the control groupⅡafter treatment has no statistical significance (P>0.05); Comparison among the three groups, the treatment group and control groupⅠ、Ⅱgroup control had significant differences (P<0.01), while the two control groups did not differ between the effect (P>0.05). The data of electropuncture combined with warm needling method group in terms of serum cytokine levels, significantly superior to the control group.
5. Comparaion of curative effect of the three groups after treatment.
After treatment, the total effective rate of treatment group was 92.9%, total effective rate of the control groupⅠwas 70.4%, total effective rate of the control groupⅡwas 65.4%, indicating that the effective rate of treatment group was significantly higher than the control group. Statistical differences among the three groups had significance (P<0.05). Statistical results indicate that the use of electropuncture combined with warm needling method treatment of KOA patients, significantly better than using electropuncture treatment and oral medicine.
6. Comparasion of adverse reactions of the three groups after treatment.
Throughout the study, the electropuncture combined with warm needling method group and the electropuncture group had no case of adverse reactions, while 1 patient had headache and 5 patients of the Celebrex group had gastrointestinal symptoms. Three groups of patients, were not found liver and kidney dysfunction, inhibition of blood and signs and symptoms of gastrointestinal bleeding after 4 weeks of treatment.
Conclusion
Clinical observation confirmed that acupuncture can enhance a sense of EA to promote the blood running, eliminate inflammatory edema, has a strong central analgesic effect; The temperature of the thermal effects produced by warm needling method, can promote blood circulation, improve the effectiveness of local tissue metabolism. Therefore, the combination of the two treatments used in KOA can indeed play a role in promoting qi and blood circulation and warming channel and expelling cold, reduce swelling and alleviate pain, improve joint function. The results show that electropuncture combined with warm needling method in treating KOA, not only can ease the physical discomfort of patients, the quality of life such as their emotions, vitality, activity of daily life is also improved even more significantly. Moreover obvious side effects had reported. In addition, according to the tips of decreasing IL-1、TNF-αof patients under treatment, we suggest that the mechanism of acupuncture treatment of KOA may be in relation to reduce excess IL-1、TNF-αlevels. Therefore it can delay osteoarthritis development, and reduce joint osteophyte formation.
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