基础医学与临床 ›› 2023, Vol. 43 ›› Issue (1): 159-164.doi: 10.16352/j.issn.1001-6325.2023.01.0159

• 研究论文 • 上一篇    下一篇

丹酚酸B减轻骨关节炎模型大鼠软骨组织损伤

骞立刚, 孙博, 于泊, 陈康, 马铮, 陈涛平, 王云飞*   

  1. 河北大学附属医院 骨科,河北 保定 071000
  • 收稿日期:2022-02-23 修回日期:2022-06-29 发布日期:2022-12-27
  • 通讯作者: *dhdssb8@163.com

Salvianolic acid B alleviates cartilage tissue damage in rat models with osteoarthritis

QIAN Ligang, SUN Bo, YU Bo, CHEN Kang, MA Zheng, CHEN Taoping, WANG Yunfei*   

  1. Department of Orthopedics, the Affiliated Hospital of Hebei University, Baoding 071000, China
  • Received:2022-02-23 Revised:2022-06-29 Published:2022-12-27
  • Contact: *dhdssb8@163.com

摘要: 目的 探究丹酚酸B对骨关节炎模型大鼠的软骨组织损伤、低氧诱导因子-1(HIF-1)和血管内皮生长因子(VEGF)的影响。方法 构建骨关节炎模型大鼠,大鼠随机分为假手术组、骨关节炎组[切断交叉韧带法(ACLT)]、尼美舒利组、丹酚酸B高(40 mg/kg)和低(10 mg/kg)剂量组及丹酚酸B+HIF-1激活组,每组12只。显微CT机检测关节处骨结构;番红固绿染色和Masson染色观察软骨组织病理学变化;检测血清白介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)含量、诱导性一氧化氮合酶(iNOS)的活性;Western blot检测软骨组织HIF-1、VEGF、基质金属蛋白酶13(MMP-13)及活化的半胱氨酸天冬氨酸蛋白酶3(ceaved caspase-3)表达。结果 与假手术组相比,骨关节炎组软骨组织损伤严重,踝骨骨体积分数(BV/TV)降低,踝骨表面积与骨体积比值(BSA/BV)、血清中IL-6、TNF-α含量、iNOS活性、软骨HIF-1、VEGF、MMP-13及cleaved caspase-3蛋白表达升高(P<0.05);与骨关节炎组相比,尼美舒利组、丹酚酸B高和低剂量组软骨组织逐渐恢复,踝骨BV/TV升高,BSA/BV、血清IL-6、TNF-α含量、iNOS活性、软骨HIF-1、VEGF、MMP-13和cleaved caspase-3蛋白表达量降低(P<0.05);与丹酚酸B高剂量组相比,丹酚酸B+HIF-1激活组软骨组织损伤加重,踝骨BV/TV降低,BSA/BV、血清IL-6、TNF-α含量、iNOS活性、软骨HIF-1、VEGF、MMP-13及cleaved caspase-3蛋白表达升高(P<0.05)。结论 丹酚酸B可通过调控HIF-1/VEGF通路,抑制HIF-1、VEGF表达,缓解骨关节炎。

关键词: 切断交叉韧带法, 骨关节炎, 丹酚酸B, 低氧诱导因子-1, 血管内皮生长因子

Abstract: Objective To explore whether salvianolic acid B affects cartilage tissue damage, hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) in osteoarthritis rats. Methods A rat model of osteoarthritis was constructed, and rats were randomly divided into sham operation group, osteoarthritis group(anterior cruciate ligment transection, ACLT), nimesulide group, salvianolic acid B high (40 mg/kg), and low (10 mg/kg) dose salvianolic acid B group, and salvianolic acid B+HIF-1 activation group, with 12 rats in each group. The bone structure at the joints of the rats in each group was measured and analyzed by micro-CT machine; The histopathological changes of cartilage were observed by safranin fast green staining and Masson staining; The contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and the activity of inducible nitric oxide syn- thase (iNOS) in rats were measured; The expression levels of HIF-1, VEGF, matrix metalloproteinase 13 (MMP-13) and activated caspase-3 (cleaved caspase-3) in rat cartilage tissue were measured by Western blot. Results Compared with the sham operation group, the cartilage tissue damage of the rats in the osteoarthritis group was severe, and the bone volume fraction (BV/TV) of the ankle bone was decreased, the ratio of ankle bone surface area to bone volume (BSA/BV), serum IL-6, TNF-α contents, iNOS activity, cartilage HIF-1, VEGF, MMP-13, and cleaved caspase-3 protein expression were increased (P<0.05); Compared with the osteoarthritis group, the cartilage tissue of the nimesulide group, the salvianolic acid B high and low dose salvianolic acid B group gradually recovered, and the ankle BV/TV was increased, BSA/BV, serum IL-6, TNF-α contents, iNOS activity, cartilage HIF-1, VEGF, MMP-13, and cleaved caspase-3 protein expression were decreased (P<0.05); Compared with the high-dose salvianolic acid B group, the salvianolic acid B+HIF-1 activation group had increased cartilage tissue injury, and ankle BV/TV was lower, BSA/BV, serum IL-6, TNF-α contents, iNOS activity, cartilage HIF-1, VEGF, MMP-13, and cleaved caspase-3 protein expression were increased (P<0.05). Conclusions Salvianolic acid B can inhibit the expression of HIF-1 and VEGF and relieve osteoarthritis by regulating the HIF-1/VEGF pathway.

Key words: anterior cruciate ligment transection, osteoarthritis, salvianolic acid B, hypoxia-inducible factor-1, vascular endothelial growth factor

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