中国组织工程研究

中国组织工程研究 ›› 2021, Vol. 25 ›› Issue (32): 5155-5161.doi: 10.12307/2021.218

• 软骨组织构建 cartilage tissue construction • 上一篇    下一篇

红姜提取物保护早期膝骨关节炎模型大鼠的关节软骨

罗  臻1，2，李宏栩1，卢启贵3，余  瑾1，余  翔2，李飞龙1，2，柴生颋1，2   

  1. 1广州中医药大学，广东省广州市   510240；2广州中医药大学第三附属医院骨科，广东省广州市   510006；3上海中医药大学深圳医院/深圳市罗湖区中医院，广东省深圳市   518000
  • 收稿日期:2020-12-11 修回日期:2020-12-18 接受日期:2021-01-27 出版日期:2021-11-18 发布日期:2021-07-26
  • 通讯作者: 余瑾，博士，教授，广州中医药大学，广东省广州市 510240
  • 作者简介:罗臻，男，1994年生，河南省潢川县人，汉族，广州中医药大学毕业，硕士，主要从事中医药治疗骨伤科疾病研究
  • 基金资助:
    广东省中医药管理局科研项目(20202085)，项目负责人：李飞龙；国家自然科学基金面上项目(81473743)，项目负责人：余瑾；深圳市科创委2020年基础研究面上项目(JCYJ20190812170815559)，项目负责人：卢启贵

Protective effect of red ginger extract on articular cartilage of rats with early knee osteoarthritis

Luo Zhen1, 2, Li Hongxu2, Lu Qigui3, Yu Jin2, Yu Xiang2, Li Feilong1, 2, Chai Shengting1, 2   

  1. 1Guangzhou University of Chinese Medicine, Guangzhou 510240, Guangdong Province, China; 2Department of Orthopedics, Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China; 
  • Received:2020-12-11 Revised:2020-12-18 Accepted:2021-01-27 Online:2021-11-18 Published:2021-07-26
  • Contact: Yu Jin, MD, Professor, Department of Orthopedics, Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
  • About author:Luo Zhen, Master, Guangzhou University of Chinese Medicine, Guangzhou 510240, Guangdong Province, China; Department of Orthopedics, Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
  • Supported by:
    the Research Project of Guangdong Provincial Administration of Traditional Chinese Medicine, No. 20202085 (to LFL); the National Natural Science Foundation of China, No. 81473743 (to YJ); the Basic Research Project of Shenzhen Science and Technology Innovation Commission in 2020, No. JCYJ20190812170815559 (to LQG)

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摘要：

红姜(Zingiber officinale Roscoe var rubrum)：是生姜的一种变种，主要产于印度尼西亚、马来西亚和中国四川等地，被广泛应用于传统医学。红姜可以显著减轻关节炎疼痛，在传统医学中常被用作治疗关节炎的经验用药。
Col2α1：膝关节软骨以及软骨与软骨下骨交界处存在的一种Ⅱ型胶原纤维α1链的基因，其表达水平的变化在软骨退化中起重要作用。

背景：研究报道，联合使用姜提取物降低血清促炎细胞因子白细胞介素1β、白细胞介素6、肿瘤坏死因子α等水平与膝骨关节炎中软骨损伤的减轻有关。
目的：观察红姜提取物灌胃对早期膝骨关节炎大鼠关节软骨保护情况及血清白细胞介素1β、白细胞介素6、肿瘤坏死因子α和软骨Col2α1 mRNA水平表达的影响，探讨红姜提取物对早期膝骨关节炎大鼠关节软骨保护作用及可能机制。
方法：将50只SPF级SD大鼠随机分为空白组、模型组、红姜低剂量组、红姜高剂量组、阳性对照组，每组各10只。除空白组外，其余40只大鼠膝关节腔注射4%木瓜蛋白酶0.2 mL+0.03 mol/L的L-半胱氨酸混合溶液，建造膝骨关节炎模型。空白组与模型组常规饲养；红姜低剂量组、红姜高剂量组、阳性对照组分别予50 mg/kg的红姜提取物水溶液、100 mg/kg红姜提取物水溶液、18 mg/kg的塞来昔布胶囊水溶液灌胃，所有干预每日1次，共持续4周。治疗4周后取大鼠膝关节软骨进行番红O-固绿染色，并对关节软骨行Mankin评分，检测血清中白细胞介素1β、白细胞介素6、肿瘤坏死因子α及软骨中Col2α1 mRNA表达水平。实验方案经广州中医药大学动物实验伦理委员会批准，批准号：20190917002。
结果与结论：①膝关节软骨的病理切片显示，模型组及各治疗组均有软骨基质流失，各治疗组Mankin评分均比空白组评分高(P < 0.05)，比模型组评分低(P < 0.05)，其中红姜高剂量组与阳性对照组评分差异无显著性意义(P > 0.05)，均显著低于红姜低剂量组(P < 0.05)；②血清白细胞介素1β、白细胞介素6、肿瘤坏死因子α结果显示，阳性对照组、红姜高剂量组、红姜低剂量组均比空白组表达上调(P < 0.05)，均比模型组表达下调(P < 0.05)，且各治疗组间水平阳性对照组<红姜高剂量组<红姜低剂量组(P < 0.05)；③软骨中Col2α1 mRNA结果显示，空白组与红姜高剂量组、阳性对照组的Col2α1 mRNA表达差异无显著性意义(P > 0.05)，模型组和红姜低剂量组Col2α1 mRNA表达相较其他3组均显著上调(P < 0.05)；④结果说明，红姜提取物可能主要通过抑制白细胞介素1β、白细胞介素6、肿瘤坏死因子α等炎症因子的表达，达到了保护膝骨关节炎关节软骨作用，从而延缓膝骨关节炎的发展进程；且相对于低剂量组，红姜提取物高剂量组的抗炎效果更好。

https://orcid.org/0000-0003-1918-0171 (罗臻)
中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程


关键词: 膝骨关节炎, 红姜, 炎性细胞因子, 软骨, 大鼠, 模型, 动物

Abstract: BACKGROUND: Studies have reported that the combined use of ginger extract to reduce the levels of serum pro-inflammatory cytokines, including interleukin-1β, interleukin-6, tumor necrosis factor-α,  is related to the reduction of cartilage injury in knee osteoarthritis.
OBJECTIVE: To observe the protective effect of red ginger extract on articular cartilage and the expression of serum interleukin-1β, interleukin-6, tumor necrosis factor-α and cartilage tissue type II collagen α1 mRNA in rats with early knee osteoarthritis, and to explore the protective effect of red ginger extract on articular cartilage of rats with early knee osteoarthritis and its possible mechanism.
METHODS: Fifty SPF Sprague-Dawley rats were randomly divided into blank group, model group, low-dose red ginger, high-dose red ginger and positive control group (n=10 per group). Except for the blank group, the rats in the other four groups were used to prepare knee osteoarthritis models by intraarticular injection of 4% papain 0.2 mL+0.03 mol/L L-cysteine mixed solution. The rats in the blank and model groups were fed routinely, and the low-dose red ginger, high-dose red ginger and positive control groups were given 50 mg/kg red ginger extract aqueous solution, 100 mg/kg red ginger extract aqueous solution and 18 mg/kg celecoxib capsule aqueous solution respectively. All the interventions were conducted once a day, for 4 continuous weeks. Four weeks after treatment, the rats in each group were killed and the knee joints were stained with safranin O-fast green. The articular cartilage was scored by Mankin scoring. The expression levels of interleukin-1β, interleukin-6, tumor necrosis factor-α in serum and type II collagen α1 mRNA in cartilage were detected. The study protocol was approved by the Animal Ethics Committee of Guangzhou University of Chinese Medicine, with an approval No. 20190917002.
RESULTS AND CONCLUSION: The pathological section of knee cartilage showed that there was cartilage matrix loss in the model and each treatment group, and the Mankin score of each treatment group was significantly higher than that of the blank group (P < 0.05) and lower than that of the model group (P < 0.05). There was no significant difference between the high-dose group and the positive control group (P > 0.05), but the scores of the two groups were lower than that of the low-dose group. The levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were upregulated in the positive control group, high-dose red ginger group and low-dose red ginger group compared with the blank group and down-regulated compared with the model group (P < 0.05). Moreover, and the levels of these cytokines were ranked as follows: positive control group < high-dose red ginger group < low-dose red ginger group (P < 0.05). The level of type II collagen α1 mRNA in cartilage showed no significant difference between the blank group and the high-dose red ginger group and the positive control group (P > 0.05), whereas the expression of type II collagen α1 mRNA was significantly increased in the model group and low-dose red ginger group compared with the other three groups (P < 0.05). To conclude, red ginger extract may protect the articular cartilage of knee osteoarthritis by inhibiting interleukin-1β, interleukin-6, and tumor necrosis factor-α, thereby delaying the development of knee osteoarthritis. Compared with the low-dose group, high-dose red ginger extract has better anti-inflammatory effect.

Key words: knee osteoarthritis, red ginger, inflammatory cytokine, cartilage, rat, model, animal

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