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舒筋健腰丸对新西兰兔膝骨关节炎模型软骨组织的影响

2020-04-16李瑞鹏陈迪新郭秋平倪庆纯周玖瑶

中国当代医药 2020年7期
关键词:细胞因子骨关节炎

李瑞鹏 陈迪新 郭秋平 倪庆纯 周玖瑶

[摘要]目的 研究舒筋健腰丸對兔膝骨关节炎模型软骨组织的影响。方法 适应性喂养1周后,随机选取12只新西兰兔作为假手术组。其余动物采用手术致软骨缺损制备骨关节炎模型,造模4周后将造模动物随机分为模型组,盐酸氨基葡萄糖组(阳性对照),舒筋健腰丸低、中、高剂量组,每组12只,雌雄各半。分组后开始灌胃给药,每天1次,连续给药28 d。通过检测膝关节活动范围、局部压痛阈值、全血黏度、关节腔冲洗液炎症因子和软骨组织病理,研究舒筋健腰丸对骨关节炎的治疗作用及作用机制。结果 舒筋健腰丸中、高剂量组的膝关节活动范围和局部压痛阈值均高于模型组,全血黏度和关节腔内白介素1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和前列腺素E2(PGE2)水平均低于模型组,差异有统计学意义(P<0.05)。盐酸氨基葡萄糖组、舒筋健腰丸高剂量组的关节软骨评分均低于模型组,差异有统计学意义(P<0.05)。结论 舒筋健腰丸对骨关节炎具有一定的治疗作用,改善血液流变学,降低关节腔内炎症因子而保护软骨可能是其作用机制。

[关键词]舒筋健腰丸;骨关节炎;细胞因子;组织病理;兔

[中图分类号] R969.4          [文献标识码] A          [文章编号] 1674-4721(2020)3(a)-0014-04

Effect of Shujin Jianyao Pills on articular cartilage of New Zealand rabbit knee osteoarthritis models

LI Rui-peng1,2,3   CHEN Di-xin1   GUO Qiu-ping1   NI Qing-chun1▲   ZHOU Jiu-yao2

1. Drug Nonclinical Evaluation and Research Center of Guangzhou General Pharmaceutical Research Institute Co., Ltd., Guangdong Province, Guangzhou   510240, China; 2. Postdoctoral Research Station of Guangzhou University of Chinese Medicine, Guangdong Province, Guangzhou   510105, China; 3. Postdoctoral Research Station of Guangzhou Pharmaceutical Group Co., Ltd., Guangdong Province, Guangzhou   510130, China

[Abstract] Objective To study the effect of Shujin Jianyao Pills on articular cartilage of New Zealand rabbit knee osteoarthritis model. Methods After one week of adaptive feeding, 12 New Zealand rabbits were randomly selected as the sham operation group. The osteoarthritis models were prepared by articular cartilage defect caused by surgery in other animals. After 4 weeks of modeling, the animals were randomly divided into model group, glucosamine hydrochloride group (positive control), Shujin Jianyao Pills low, middle and high dose groups, 12 cases in each group, half male and half female. After grouping, the animals were intragastrically administrated with drugs once daily for 28 days. The therapeutic effect and mechanism of Shujin Jianyao Pills on osteoarthritis were studied by detecting the range of knee joint activity, local tenderness threshold, whole blood viscosity, inflammatory cytokines of articular cavity flushing fluid and articular cartilage histopathology. Results The knee joint range and local tenderness threshold of the waist in the Shujin Jianyao Pills middle and high dose groups were higher than those in the model group, the whole blood viscosity and interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2) levels in articular cavity were lower than those in the model group, and the differences were statistically significant (P<0.05). The articular cartilage scores of the glucosamine hydrochloride group and the Shujin Jianyao Pills high dose group were lower than those of the model group, and the differences were statistically significant (P<0.05). Conclusion Shujin Jianyao Pills have a certain therapeutic effect on osteoarthritis. Improving hemorheology, reducing inflammatory cytokines in articular cavity and protecting articular cartilage may be the mechanism of its action.

模型组关节腔冲洗液IL-1β、TNF-α和PGE2水平均高于假手术组,差异有统计学意义(P<0.05);盐酸氨基葡萄糖组及舒筋健腰丸低、中、高剂量组关节腔冲洗液IL-1β、TNF-α水平均低于模型组,盐酸氨基葡萄糖组及舒筋健腰丸中、高剂量组关节腔冲洗液PGE2水平均低于模型组,差异有统计学意义(P<0.05)(表3)。

3讨论

OA多发于老年人群,累及膝关节、髋关节等部位,造成关节软骨退行性变。流行病学调查显示,我国约有3%的人患有OA,并且随着年龄增加,发病率也随之增加[7]。OA发病机制尚不清楚,但其主要病理变化为关节软骨的退行性变、反应性关节边缘骨赘形成等[8-9]。目前临床上OA缺乏有效的治療方法,使得患者病情日益严重,给社会造成沉重的经济负担[10-11]。

中医认为,OA属于痹症,气血不足,肝肾亏虚,风、寒、湿侵入骨髓,痹阻经络导致筋骨失养而发病[12]。舒筋健腰丸主要由补益肝肾、强筋健骨的中药组成,方中金毛狗脊强腰膝、补肝肾、祛风湿,为君药;黑老虎行气散瘀、通络止痛,桑寄生补肝肾、祛风湿,鸡血藤补血活血通络,千斤拔祛风除湿,牛大力舒筋活络,金樱子固精滋肾,以上共为臣药;女贞子、菟丝子补益肝肾,两面针祛风通络,胜湿止痛,延胡索、乳香、没药共同发挥活血祛瘀止痛功效,为佐使之药。根据中医理论,舒筋健腰丸可用于OA的治疗。

研究表明,舒筋健腰丸对腰椎间盘突出和坐骨神经痛具有较好的疗效[13-14]。本研究结果提示,舒筋健腰丸中、高剂量可明显扩大模型动物膝关节的活动范围,提高模型动物膝关节局部压痛阈值,降低低切、中切与高切状态下血液的黏度,从而改善OA关节僵硬和疼痛的症状。舒筋健腰丸高剂量还可减轻模型动物关节软骨病理评分,促进纤维软骨修复。

IL-1β和TNF-α是与关节软骨破坏相关的炎症因子。IL-1β可抑制软骨细胞合成蛋白聚糖、Ⅱ型胶原,导致软骨细胞变性[15-16]。TNF-α既可协同增加IL-1β的作用,还可刺激软骨细胞产生一氧化氮,诱导软骨细胞凋亡[17-18]。本研究结果提示,舒筋健腰丸低、中、高剂量均可降低模型动物关节腔冲洗液中IL-1β、TNF-α水平。

PGE2主要参与诱发炎症反应,促进局部血管扩张,使毛细血管通透性增强,引起疼痛症状[19]。本实验结果提示,舒筋健腰丸中、高剂量可降低模型动物关节腔冲洗液PGE2水平,从而发挥抗炎镇痛作用。

综上所述,舒筋健腰丸对OA模型有一定的治疗作用,改善血液流变学,降低关节腔内炎症因子水平而保护关节软骨可能是其作用机制。

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[14]厉强,刘文东,于鹏飞.舒筋健腰丸治疗腰椎间盘突出所致坐骨神经痛(肝肾亏虚证)的临床研究[J].中药材,2018,41(3):737-739.

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(收稿日期:2019-07-12  本文编辑:任秀兰)

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