中国组织工程研究 ›› 2017, Vol. 21 ›› Issue (8): 1167-1171.doi: 10.3969/j.issn.2095-4344.2017.08.004

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

常山酮阻止早期骨性关节炎的关节软骨退变

李  蛟,胥伯勇,郭文涛,穆文博,张振东,纪保超,曹  力   

  1. 新疆医科大学第一附属医院关节外科,新疆维吾尔自治区乌鲁木齐市   830000
  • 收稿日期:2016-11-18 出版日期:2017-03-18 发布日期:2017-04-14
  • 通讯作者: 曹力,主任医师,新疆医科大学第一附属医院关节外科,新疆维吾尔自治区乌鲁木齐市 830000
  • 作者简介:李蛟,男,1990年生,陕西省西乡县人,汉族,新疆医科大学在读硕士,主要从事骨与关节疾病的研究。
  • 基金资助:

    新疆维吾尔自治区科技项目重大专项计划(201430123-3)

Halofuginone delays articular cartilage degeneration in early osteoarthritis 

Li Jiao, Xu Bo-yong, Guo Wen-tao, Mu Wen-bo, Zhang Zhen-dong, Ji Bao-chao, Cao Li   

  1. Department of Joint Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi 83000, Xinjiang Uygur Autonomous Region, China
  • Received:2016-11-18 Online:2017-03-18 Published:2017-04-14
  • Contact: Cao Li, Chief physician, Department of Joint Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi 83000, Xinjiang Uygur Autonomous Region, China
  • About author:Li Jiao, Studying for master’s degree, Department of Joint Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi 83000, Xinjiang Uygur Autonomous Region, China
  • Supported by:

    the Major Program of the Xinjiang Uygur Autonomous Region Science and Technology Project, No. 201430123-3

摘要:

文章快速阅读:

文题释义:
常山酮:是一种生物碱,是中药有效成分常山碱的衍生物,其分子式是 C16H17BrCIN3O3 •HBr,为白色或淡灰色结晶性粉末,无臭,味苦。关于常山酮的研究已经有数十年了,很长一段时间其一直作为广谱抗球虫药使用。近年来,随着对常山酮的深入研究,发现常山酮可促进伤口修复、抑制组织纤维化 。
透明软骨:分布较广,成体的关节软骨、肋软骨及呼吸道的一些软骨均属这种软骨。新鲜时呈半透明状,较脆,易折断。透明软骨间质中的纤维为胶原原纤维,含量较少,基质较丰富。陷窝周围有一层含硫酸软骨素较多的基质,称软骨囊(cartilage capsule),染色时呈强嗜碱性。软骨细胞在软骨内的分布有一定规律,靠近软骨膜的软骨细胞较幼稚,体积小,呈扁圆形,单个分布;位于软骨中部的软骨细胞接近圆形,成群分布,每群有2-8个细胞,它们是由一个细胞分裂增生而成,故称同源细胞群。
摘要
背景:
研究证实,常山酮能够减弱骨性关节炎病程发展的进程。
目的:进一步验证常山酮对早期骨性关节炎的防治作用。
方法:健康C57BL6J雄性小鼠45只,随机分为3组,每组15只,假手术组只打开小鼠右膝关节囊不损伤其他部位,术后不做处理;其余小鼠均切断小鼠右膝前交叉韧带造骨性关节炎模型,安慰剂组造模后第3天开始给予蒸馏水灌胃每天1次;常山酮组造模后第3天开始按0.5 mg/kg剂量灌胃,每天1次,28 d后处死小鼠取右膝关节,做苏木精-伊红染色和番红固绿染色观察关节组织的形态和结构;免疫组织化学检测转化生长因子β1的表达量。
结果与结论:①组织学观察,假手术组关节软骨结构正常,潮线清晰,细胞排列整齐,未有软骨表面磨损痕迹;安慰剂组关节软骨层明显变薄,甚至部分损伤至潮线,软骨表面磨损严重并有碎裂现象,细胞排列紊乱;常山酮组软骨细胞分层较清晰且排列较整齐, 潮线清晰,细胞形态较规则;②3组透明软骨厚度假手术组 >山酮组>安慰剂组,钙化软骨厚度假手术组<常山酮组<安慰剂组,透明软骨厚度/钙化软骨假手术组>常山酮组>安慰剂组;③OARSI评分常山酮组显著低于安慰剂组,转化生长因子β1阳性细胞/软骨细胞值常山酮组显著低于安慰剂组,2项指标3 组间比较差异均有显著性意义(P < 0.05);④结果表明,常山酮灌胃能部分阻止小鼠早期骨性关节炎关节软骨退变,其作用机制可能是降低转化生长因子β1的表达,从而延缓骨性关节炎的进展。

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
ORCID: 0000-0001-9521-149X(李蛟)

关键词: 组织构建, 软骨组织工程, 常山酮, 骨性关节炎, 软骨细胞, 关节软骨, 透明软骨, 钙化软骨, 转化生长因子β1

Abstract:

BACKGROUND: Halofuginone has been proved to ameliorate the pathogenesis of osteoarthritis.
OBJECTIVE: To further verify the protective effect of halofuginone on early osteoarthritis.
METHODS: Forty-five healthy male C57BL6J mice were randomly divided into three groups (n=15 per group): the mice in sham operation group were only subjected to right knee capsulotomy; in the other two groups, animal models of osteoarthritis were established by cutting off the right anterior cruciate ligament, followed by treated with distilled water (placebo group) or 0.5 mg/kg halofuginone (halofuginone group) via gavage, once daily beginning at 3 days after modeling. Twenty-eight days after treatment, all mice were sacrificed and the right knee was removed. The morphology and structure of the joint tissue were observed by hematoxylin-eosin staining and safranin fast green staining; the expression of transforming growth factor-β1 (TGF-β1) was detected by immunohistochemistry.
RESULTS AND CONCLUSION: The structure of articular cartilage in the sham operation group was normal, the cells arranged in neat rows, and the articular surface was not worn. In the placebo group, the articular cartilage layer became thinner, the cartilage surface was worn and even fragmented, and cells arranged in disorder. In the halofuginone group, the cartilage cell layer was clear and tidy, with regular cell morphology. The hyaline cartilage thickness and hyaline cartilage thickness/calcified cartilage thickness were ranked as follows: sham operation group > halofuginone group > placebo group. The calcified cartilage thickness was the highest in the placebo group, followed by halofuginone group, and lowest in the sham operation group. Osteoarthritis Research Society International scores and TGF-β1 positive cells/chondrocytes in the halofuginone group were significantly lower than those in the placebo group, and all above indices showed significant differences among groups (P < 0.05). These results suggest that halofuginone via gavage can partially prevent articular cartilage degeneration in early osteoarthritis mice probably by downregulating the expression of TGF-β1, thus delaying the progression of osteoarthritis.

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

Key words: Osteoarthritis, Cartilage, Transforming Growth Factor beta1, Tissue Engineering

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