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Volume 38 Issue 4
Jul.  2020
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LI Pengfei, JIAN Qiang, QIAO Meina, SUN Changgui, GAO Junfeng. The clinical effect of Yaotongning capsule combined with etoricoxib in the treatment of lumbar pain and inflammatory status in elderly patients with lumbar osteoarthritis[J]. Journal of Pharmaceutical Practice and Service, 2020, 38(4): 368-372. doi: 10.12206/j.issn.1006-0111.201912170
Citation: LI Pengfei, JIAN Qiang, QIAO Meina, SUN Changgui, GAO Junfeng. The clinical effect of Yaotongning capsule combined with etoricoxib in the treatment of lumbar pain and inflammatory status in elderly patients with lumbar osteoarthritis[J]. Journal of Pharmaceutical Practice and Service, 2020, 38(4): 368-372. doi: 10.12206/j.issn.1006-0111.201912170

The clinical effect of Yaotongning capsule combined with etoricoxib in the treatment of lumbar pain and inflammatory status in elderly patients with lumbar osteoarthritis

doi: 10.12206/j.issn.1006-0111.201912170
  • Received Date: 2019-12-30
  • Rev Recd Date: 2020-03-05
  • Available Online: 2020-07-27
  • Publish Date: 2020-07-25
  •   Objective  To study the clinical effect of Yaotongning capsule combined with etoricoxib for the pain and inflammation of lumbar vertebrae in elderly patients with lumbar osteoarthritis.  Methods  120 elderly patients with lumbar osteoarthritis admitted to our hospital from January 2016 to June 2018 were randomly divided into the control group and the observation group, with 60 patients in each group. Patients in the control group were treated with etoricoxib, while patients in the observation group were treated with etoricoxib plus Yaotongning capsule orally. Both groups received medications for 2 weeks. Spinal pain and quality of life score changes were recorded. The inflammatory cytokines in serum TNF-α, GM-CSF, COX-2 and BMP-2 levels were monitored. The clinical efficacy was compared and drug safety profile was evaluated for two groups.  Results  The effective rates of the control group and the observation group were 78.33% and 91.67% respectively. The effective rate in the observation group weas significantly higher (P<0.05). After treatment, the VAS score for the patients in the observation group was significantly lower than that in the control group (P<0.05). The SF-36 score in the observation group was significantly increased (P<0.05), and the levels of TNF-α,GM-CSF and COX-2 in the serum were significantly lower than those in the control group (P<0.05), and the levels of BMP-2 were significantly increased (P<0.05).  Conclusion  Yaotongning capsule combined with etoricoxib in the treatment of senile lumbar osteoarthritis has definite curative effect. It significantly reduced lumbar pain, improved quality of life, inhibited inflammatory reaction, and had a better drug safety profile. The further clinical investigation for the combination therapy is warranted.
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    [2] GOODE A P, NELSON A E, KRAUS V B, et al. Biomarkers reflect differences in osteoarthritis phenotypes of the lumbar spine: the Johnston County Osteoarthritis Project[J]. Osteoarthr Cartil,2017,25(10):1672-1679. doi:  10.1016/j.joca.2017.07.007
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    [9] 徐昌, 高健, 王小挺, 等. 自拟补肾通络方治疗腰椎骨性关节炎44例[J]. 环球中医药, 2018, 11(10):1589-1591. doi:  10.3969/j.issn.1674-1749.2018.10.024
    [10] 张静, 杨晓利, 张竞, 等. 腰痛宁胶囊对腰椎骨性关节炎患者血清IL-1β、TGF-β1的影响[J]. 中成药, 2015, 37(4):916-918. doi:  10.3969/j.issn.1001-1528.2015.04.053
    [11] 张立国, 赵丽丽, 倪力军, 等. 腰痛宁胶囊有效部位组合对IL-1β诱导大鼠滑膜细胞增殖及IL-6的影响[J]. 中国现代中药, 2015, 17(9):922-926.
    [12] 薄云, 李淑贤, 赵丽艳, 等. 疏肝滋肾汤治疗腰椎骨性关节炎的疗效观察[J]. 中华中医药杂志, 2017, 32(10):4762-4764.
    [13] 贾涛, 刘盾, 赖福崇, 等. 中药内服治疗腰椎骨性关节炎近10年文献潜在用药规律探讨[J]. 世界中医药, 2018, 13(12):3212-3218. doi:  10.3969/j.issn.1673-7202.2018.12.061
    [14] 陈方芳, 谯智泉, 罗永浩. 新力正骨喷雾剂中药离子导入联合针灸治疗颈椎骨性关节炎的临床观察[J]. 中国医药导刊, 2016, 18(11):1137-1138.
    [15] 余扬, 崔磊. 膝骨性关节炎软骨组织低氧诱导因子1α和粒细胞-巨噬细胞集落刺激因子的表达[J]. 中国组织工程研究, 2015, 19(11):1683-1687. doi:  10.3969/j.issn.2095-4344.2015.11.009
    [16] KAY A G, DALE T P, AKRAM K M, et al. BMP2 repression and optimized culture conditions promote human bone marrow-derived mesenchymal stem cell isolation[J]. Regen Med,2015,10(2):109-125. doi:  10.2217/rme.14.67
    [17] 洪振强, 高弘建, 苏友新, 等. 马钱子总碱对兔膝骨关节炎模型软骨损伤修复作用及机制[J]. 中国中西医结合杂志, 2018, 38(8):991-996. doi:  10.7661/j.cjim.20180626.183
    [18] 张立国, 程佳佳, 倪力军, 等. 以生物碱为主要部位的7种腰痛宁衍生方的细胞抗炎、免疫活性比较及优选组方的体内药效评价[J]. 中草药, 2016, 47(6):963-969.
    [19] 张泽峰, 王晶, 孙艺茹, 等. 土鳖虫醇提物制备方法及其制备物对MC3T3-E1成骨细胞促增殖作用活性评价[J]. 辽宁中医药大学学报, 2018, 20(7):50-54.
    [20] 宁张弛, 宋志前, 刘元艳, 等. 不同提取方式对醋乳香中主要乳香酸类成分含量及其抗炎活性的影响[J]. 中国实验方剂学杂志, 2017, 23(22):14-19.
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The clinical effect of Yaotongning capsule combined with etoricoxib in the treatment of lumbar pain and inflammatory status in elderly patients with lumbar osteoarthritis

doi: 10.12206/j.issn.1006-0111.201912170

Abstract:   Objective  To study the clinical effect of Yaotongning capsule combined with etoricoxib for the pain and inflammation of lumbar vertebrae in elderly patients with lumbar osteoarthritis.  Methods  120 elderly patients with lumbar osteoarthritis admitted to our hospital from January 2016 to June 2018 were randomly divided into the control group and the observation group, with 60 patients in each group. Patients in the control group were treated with etoricoxib, while patients in the observation group were treated with etoricoxib plus Yaotongning capsule orally. Both groups received medications for 2 weeks. Spinal pain and quality of life score changes were recorded. The inflammatory cytokines in serum TNF-α, GM-CSF, COX-2 and BMP-2 levels were monitored. The clinical efficacy was compared and drug safety profile was evaluated for two groups.  Results  The effective rates of the control group and the observation group were 78.33% and 91.67% respectively. The effective rate in the observation group weas significantly higher (P<0.05). After treatment, the VAS score for the patients in the observation group was significantly lower than that in the control group (P<0.05). The SF-36 score in the observation group was significantly increased (P<0.05), and the levels of TNF-α,GM-CSF and COX-2 in the serum were significantly lower than those in the control group (P<0.05), and the levels of BMP-2 were significantly increased (P<0.05).  Conclusion  Yaotongning capsule combined with etoricoxib in the treatment of senile lumbar osteoarthritis has definite curative effect. It significantly reduced lumbar pain, improved quality of life, inhibited inflammatory reaction, and had a better drug safety profile. The further clinical investigation for the combination therapy is warranted.

LI Pengfei, JIAN Qiang, QIAO Meina, SUN Changgui, GAO Junfeng. The clinical effect of Yaotongning capsule combined with etoricoxib in the treatment of lumbar pain and inflammatory status in elderly patients with lumbar osteoarthritis[J]. Journal of Pharmaceutical Practice and Service, 2020, 38(4): 368-372. doi: 10.12206/j.issn.1006-0111.201912170
Citation: LI Pengfei, JIAN Qiang, QIAO Meina, SUN Changgui, GAO Junfeng. The clinical effect of Yaotongning capsule combined with etoricoxib in the treatment of lumbar pain and inflammatory status in elderly patients with lumbar osteoarthritis[J]. Journal of Pharmaceutical Practice and Service, 2020, 38(4): 368-372. doi: 10.12206/j.issn.1006-0111.201912170
  • 腰椎骨性关节炎(lumbar osteoarthritis,LOA)是临床常见的慢性骨关节病,好发于老年人。患者临床上多见腰痛、活动受限等症状,以腰椎椎间关节突软骨面病理退变破坏及骨质增生为特征[1]。近年来,随着我国人口老龄化的加剧,临床上LOA的发病率呈逐年升高的趋势,长期反复发作的痛感及活动受限严重影响患者的生活质量[2]。目前,临床上治疗LOA以抗炎、镇痛等对症治疗为主。依托考昔是一种新型的高选择性的环氧化酶-2抑制剂,可抗炎、止痛,在改善骨关节炎临床症状方面有一定效果,且具有易吸收、起效快、镇痛好、药效作用时间长等特点,但其单用仍无法取得根治效果[3-4]。现有研究证实,中药治疗LOA具有多靶点、整体调节的特点,能够通过影响软骨细胞凋亡与增殖、调节软骨细胞代谢、抑制炎症介质表达等多种途径对病情进行干预[5]。中医学认为,“寒”和“瘀”为LOA的主要病理基础,腰痛宁胶囊由十味中药组成,君药马钱子,臣药麻黄、苍术、乳香、没药、土鳖虫,佐药全蝎、僵蚕,使药川牛膝、甘草,君臣佐使,相辅相成,功在温经散寒、化瘀通络、消肿止痛,临床上常用于腰椎间盘疾病的诊治,效果显著,可明显改善症状,安全性较好[6]。鉴于此,本研究选取120例LOA患者作为研究对象,采用腰痛宁胶囊联合依托考昔进行协同治疗,考察其改善老年腰椎骨性关节炎痛感、炎症状态的临床效果。

  • 选取2016年1月至2018年6月就诊于本院的120例老年腰椎骨性关节炎患者,采用随机数字表法分为对照组和观察组。对照组患者60例,男34例,女26例,年龄60~75(65.37±2.42)岁,病程1~13年,平均病程(4.26±1.37)年;观察组患者60例,男35例,女25例,年龄60~75(64.85±2.37)岁,病程1~15年,平均病程(4.30±1.35)年。两组患者的一般资料经统计分析,差异均无统计学意义(P>0.05),可以进行对比。

  • (1)西医诊断符合《骨科诊疗常规》[7]中有关腰椎骨性关节炎的标准。①腰部疼痛和僵硬感,反复发作;②腰椎活动受限、转侧不利,重时可见腰弯驼背;③腰椎X线片示椎体边缘骨赘形成,间隙可变窄,肥大增生,小关节面不规则;④脊柱生理弧度正常或改变,腰骶部压痛;⑤症状以晨起明显,不能久坐,活动过多或劳累后疼痛加重,变换体位及姿势可缓解疼痛。

    (2)中医参照《中药新药临床研究指导原则》[8]中有关寒湿瘀阻证确诊。①腰部或关节疼痛、酸痛;②活动受限, 阴雨天加重;③恶寒畏冷,得温痛减;④肢体沉重。

  • ①患者年龄60~75岁,男女不限;②符合上述诊断标准;③近1个月未接受相关药物治疗;④经本院伦理委员会批准,患者签署知情同意书。

  • ①原发性骨质疏松症者;②肝肾等器质性病变、凝血系统、内分泌系统、心脑血管、免疫系统疾病患者;③合并腰椎滑脱、强直性脊柱炎、腰椎骨折、腰椎结核、腰椎椎管狭窄、脊柱侧弯、腰椎肿瘤者;④药物禁忌证者;⑤依从性、耐受性欠佳者;⑥同期参与其他临床研究者。

  • 对照组患者给予依托考昔片(国药准字J20180057,生产批号: 20150918,规格: 60 mg),每日1次,口服,60 mg/次。观察组患者则在对照组基础上加用腰痛宁胶囊(颈复康药业集团有限公司,国药准字Z13020898,规格:0.3 g)口服,4~6粒/次,每日1次,睡前0.5 h口服。两组患者均连续治疗2周。

  • ①治疗前后用疼痛视觉模拟评分(visual analogue scale,VAS)以0~10分评价腰椎痛感:无痛(0分);可耐受,轻微疼痛(1~3分);可耐受,但影响生活,中度疼痛(4~6分);不可耐受,剧痛(7~10分),评分愈低,痛感愈轻。②治疗前后用健康调查简表(SF-36)评价生活质量,重点对生理功能、生命活力、躯体疼痛、情感职能、心理健康、社会功能等方面共计8个维度、36个问题进行评价,总分 0~100分,分数越高,生活质量越好。③治疗前后抽取肘静脉血,离心后取上清液于−20 ℃待测。采用酶联免疫吸附试验(ELISA)测定血清中TNF-α、GM-CSF、COX-2、BMP-2水平,试剂购自上海逸峰生物科技有限公司,操作严格按试剂盒说明进行。

  • 参照《中药新药临床研究指导原则》[8]中相关疗效标准拟定。①临床控制:临床症状基本消失,X线片结果腰椎病变消失;②显效:临床症状明显好转,劳累后仍有疼痛,X线片显示腰椎病变明显好转;③无效:达不到上述标准,甚至病情加重。

  • 所有数据采用SPSS19.0软件统计处理,计数资料采用χ2检验,计量资料用($\bar x$±s)表示,数据符合正态分布,组间对比用独立样本t检验;以P<0.05表示差异具有统计学意义。

  • 表1显示,对照组与观察组患者的有效率分别为78.33%和91.67%,两者有效率的差异有统计学意义(P<0.05)。

    组别临床控制好转无效有效率(%)
    对照组(60例)20271378.33
    观察组(60例)3718 591.67*
      *P<0.05,与对照组比较。
  • 组内比较,治疗后两组患者的疼痛VAS评分均较治疗前明显降低(P<0.05);组间比较,观察组患者的VAS评分降低程度较对照组更为明显,差异有统计学意义(P<0.05),见表2

    组别VAS评分
    治疗前治疗后
    对照组(60例)7.26±0.455.79±0.89*
    观察组(60例)7.35±0.433.26±0.54*#
    t0.1438.027
    P>0.05<0.05
      *P<0.05,与同组治疗前比较;#P<0.05,与对照组比较。
  • 组内比较,治疗后两组患者的生活质量SF-36评分明显高于治疗前;组间比较,观察组的生活质量相关各评分明显高于对照组,差异有统计学意义(P<0.05),见表3

    评分项目对照组(60例)观察组(60例)
    治疗前治疗后治疗前治疗后
    生理功能63.73±5.6272.63±6.11*63.21±4.7791.52±10.40*#
    生命活力68.40±7.5272.44±7.10*68.87±7.3677.14±9.23*#
    躯体疼痛57.64±8.3068.32±9.07*57.85±7.4281.70±11.26*#
    情感职能54.02±6.5158.19±7.59*53.32±6.4680.36±9.20*#
    心理健康61.02±4.7965.04±5.19*60.43±5.1278.22±7.45 *#
    社会功能67.90±4.2773.18±8.39*66.85±4.3689.30±11.34 *#
      *P<0.05,与同组治疗前比较;#P<0.05,与对照组比较。
  • 治疗后,两组患者的血清中TNF-α、GM-CSF、COX-2水平均较治疗前明显降低(P<0.05),BMP-2水平则较治疗前明显升高(P<0.05),组间比较,观察组患者炎性因子水平优于对照组,差异有统计学意义(P<0.05),见表4

    检测项目对照组(60例)观察组(60例)
    治疗前治疗后治疗前治疗后
    TNF-α(μg/L)105.77±15.6982.47±10.36*105.32±17.5841.30±7.18*#
    GM-CSF (μmol/L)1.69±0.341.09±0.21*1.70±0.310.35±0.04 *#
    COX-2(pg/ml)26.82±3.1717.64±2.77*26.73±3.2110.20±1.23*#
    BMP-2(ng/L)82.74±11.93120.42±13.29*81.85±13.67175.57±22.50*#
      *P<0.05,与同组治疗前比较;#P<0.05,与对照组比较。
  • 中医学认为,LOA属于 “痹证”、“腰痛”等范畴,其病因、病机于古文献中早有记载。《素问·脉要精微论》有曰: “腰为肾之府,转摇不能,肾将惫矣”;《中藏经》中有云:“痹者,风寒暑湿之气,中于脏腑之为也”;《素问·六元正如纪大论》中曰:“感于寒,则病人关节禁固,腰脽痛,寒湿持于气交而为疾也。”可见,LOA实为本虚标实之证,尤其是老年患者,肝肾不足,正虚而卫外不固,风、寒、湿、痰、瘀等侵袭腰部,痹阻经络,阻滞经脉,不通则痛而发[9]。寒湿内蕴、血行瘀滞是其关键病机特点,治之当遵“急则治其标”之旨,重在“散寒”、“化瘀”。本研究所用腰痛宁胶囊由马钱子粉、土鳖虫、麻黄、乳香、没药、川牛膝、全蝎、僵蚕、苍术、甘草等药物有效成分精制而成,具有消肿止痛、疏散寒邪、温经通络等功效,符合LOA“寒湿瘀阻”的病机特点。方中马钱子为伤科疗伤止痛之佳品,功可消肿止痛、通络散结;土鳖虫功在破血逐瘀、续筋接骨,善治瘀血阻络、筋骨折伤之证;麻黄辛温,轻扬上达,善散风寒,宣肺郁,通腠理,透毛窍,起到散寒通滞之效;乳香辛香走窜,善活血消肿、散瘀止痛; 没药功在活血化瘀,行气止痛;川牛膝长于补肝肾、强筋骨、化瘀通络;全蝎、僵蚕为虫类药,重在活血化瘀、消肿止痛;苍术苦温辛烈,功在祛风散寒、燥湿健脾、化浊止痛;甘草调和诸药。诸药合用,药证相应,共奏温经散寒、化瘀止痛之功。本研究表明,治疗后观察组患者的临床有效率明显高于对照组(P<0.05);且患者痛感的缓解程度更大(P<0.05),患者生活质量改善更明显(P<0.05),结果证实,加用腰痛宁胶囊联合依托考昔协同作用能更好地促进腰痛症状的缓解,提高生活质量,其效果优于单纯依托考昔治疗。现有研究证实,腰痛宁全方有良好的活血、抗炎、免疫调节、促进骨关节修复、利于软骨细胞增殖等药理活性。张静等[10]报道证实,腰痛宁胶囊可以通过抑制LOA患者IL-1β的表达,升高TGF-β1的水平而减轻炎性反应,促进软骨修复,保护关节;张立国等[11]动物实验研究证实,腰痛宁胶囊抗炎镇痛效果良好,对IL-1β诱导的大鼠软骨细胞具有显著促增殖作用,还能抑制小鼠的疼痛反应,提高痛阈,从而在减轻腰痛等症状方面收效明显,与本研究结果一致。

    现代医学认为,关节软骨无菌性炎症反应和软骨基质降解是LOA患者的主要病理特征,腰椎周围的结蹄组织在炎性物质的刺激下发生粘连,进而引起腰椎后期的关节功能障碍[12]。多种细胞因子的异常表达参与能促进关节软骨炎症、软骨降解[13]。TGF-α是由单核巨噬细胞产生的炎症性细胞因子,可加重炎症性反应,还能够刺激破骨细胞活性,抑制软骨胶原等的合成,促进骨的吸收,破坏骨质[14];GM-CSF为炎症反应的敏感标志物,是在炎症反应过程中由损伤内皮细胞释放的一种多肽类激素样的造血生长因子,具有调节细胞黏附、促进IL-炎症介质分泌等功能[15];COX-2催化能促使花生四烯酸转变为PGE2等前列腺素,引起炎症、疼痛,故而COX-2水平的增加能够加重机体炎症反应,还可加重患者疼痛感;基础研究已发现,BMP-2参与人体成骨细胞分化,是重要的骨修复因子,可营造出有助于血管化的骨组织环境,还可诱导未分化的间充质细胞趋化并分化为成骨细胞和软骨细胞[16]。本研究结果表明,观察组患者治疗后血清中TNF-α、GM-CSF、COX-2等炎症介质水平降低更明显,BMP-2水平则升高更明显(P<0.05)。这说明,腰痛宁胶囊联合依托考昔协同起效的原因,可能是其能够抑制血清中TNF-α、GM-CSF、COX-2等炎性介质的合成和释放,从而减轻关节炎症损伤;同时,还可能通过干预BMP-2等因子表达而增强关节内软骨基质的合成代谢能力,促进新骨生成,修复受损的关节软骨。分析表明临床疗效也与单味药物的药理学作用密切相关。例如,现代药理研究证实,马钱子不仅具有良好的消炎镇痛作用,还能够明显降低关节炎软骨细胞的凋亡,提升细胞增殖效率;动物实验报道证实,马钱子总碱能通过抑制软骨细胞凋亡、改善软骨代谢等途径发挥对骨关节炎软骨损伤的修复作用[17];土鳖虫、僵蚕、全蝎水提液在细胞抗炎、促进软骨细胞增殖活性模型中表现出较好的活性[18-19];乳香、没药具有显著抗炎止痛作用,尤其乳香的有效成分能显著减轻骨性关节炎患者的疼痛,增强骨关节的屈伸,减少关节部位的隆突,并有修复功能[20]

    综上所述,腰痛宁胶囊联合依托考昔协同治疗能较大程度地减轻LOA患者的腰疼痛症状,改善生活质量,尤其在进一步降低患者炎症反应介质水平、减轻关节炎症损伤、调节软骨代谢、修复受损的软骨组织等方面具有更好的效果,具有临床借鉴价值。

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