文章摘要
温经通络汤对小鼠膝骨关节炎软骨形态改变和VEGF、MMP13、HIF1α表达情况的影响
Effects of WenJingTongLuoTang on cartilage morphologic changes and vascular endothelial growth factor levels in knee osteoarthritis in mice
投稿时间:2020-04-30  录用日期:2020-05-19
DOI:
中文关键词: 温经通络汤  膝骨关节炎  血管内皮生长因子  基质金属蛋白酶13  缺氧诱导因子-1α
英文关键词: WenJingTongLuoTang  knee osteoarthritis  vascular endothelial growth factor  matrix metalloproteinases 13  hypoxia inducible factor-1α
基金项目:国家自然科学基金项目(面上项目,重点项目,重大项目)
作者单位邮编
许炜民 南京中医药大学骨伤研究所 210023
钱佳佳 南京中医药大学骨伤研究所 210023
许奇 南京中医药大学骨伤研究所 210023
韩龙 南京中医药大学骨伤研究所 210023
黄桂成* 南京中医药大学骨伤研究所 210023
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中文摘要:
      目的 观察温经通络汤对小鼠膝骨关节炎模型核血管内皮生长因子(VEGF),基质金属蛋白酶-13(MMP3),缺氧诱导因子-1α(HIF1α)的影响, 探讨其对膝骨关节炎的作用机制。方法 采用前交叉韧带离断(ACLT)法建立小鼠膝骨关节炎模型, 将30只C57BL/6小鼠随机分为假手术组(A组)、模型组(B组)、温经通络汤高剂量组(C组)、温经通络汤低剂量组(D组)、阳性药组(E组)。造模成功后A组与B组分别予以10ml/kg.d-1生理盐水灌胃,C组与D组分别予以10ml/kg.d-1温经通络汤灌胃,E组予以10ml/kg.d-1美洛昔康水溶液灌胃,持续2周。 采用组织形态学观察及Mankin’s评分评估各组小鼠膝关节表面软骨的损伤程度。采用免疫组化法观察各组膝关节表面软骨中VEGF、MMP13和HIF1α的表达水平,采用酶联免疫吸附检测各组膝关节软骨组织中血管内皮生长因子( VEGF) 、基质金属蛋白酶的表达水平。结果 组织形态学观察及Mankin’s评分显示与A组相比,其余各组的评分均明显升高(P<0.05),与B组相比,C组、D组、E组的评分则明显下降(P<0.05)。免疫组化表明C、D、E组中小鼠膝关节软骨的VEGF、MMP13、HIF1α表达相较于B组均有明显下降(P<0.05)。ELISA检测结果显示,与A组相比,其余各组的小鼠血清中VEGF、MMP13及HIF1α表达均有明显升高(P<0.05),其中B小鼠血清中VEGF、MMP13及HIF1α的表达最高,C组、D组、E组与B组相比均有下降(P<0.05)。结论 温经通络汤可能通过调控HIF1α抑制 VEGF及MMP13的表达发挥缓解及治疗膝骨关节炎的作用。
英文摘要:
      Objective: Observe the effects of WJTLT on the mouse model of knee osteoarthritis, including nucleus vascular endothelial growth factor (VEGF), matrix metalloproteinase-13 (MMP3) and hypoxia-induced factor-1α (HIF1α). Methods: 30 C57BL/6 mice were randomly divided into sham operation group (group A), model group (group B), high dose group (group C), low dose group (group D) and positive drug group (group E). After successful modeling, group A and group B received normal saline gavage of 10ml/kg.d-1, group C and group d gavage of 10ml/kg.d-1 WJTLT, and group E gavage of 10ml/kg.d-1 meloxicam aqueous solution for 2 weeks. Histological observation and Mankin"s score were used to evaluate the degree of damage of the surface cartilage of the knee joint in each group. Immunohistochemistry was used to observe the expression levels of VEGF, MMP13 and HIF1α in the surface cartilage of the knee in each group, and the expression levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase in the cartilage of the knee in each group were detected by enzyme-linked immunoadsorption. Results: Histopathological observation and Mankin"s score showed that compared with group A, the scores of other groups were significantly increased (P < 0.05), while compared with group B, the scores of group C, group D and group E were significantly decreased (P < 0.05). Immunohistochemistry showed that the expressions of VEGF, MMP13 and HIF1α in the mouse knee cartilage in group C, D and E were significantly decreased compared with those in group B (P < 0.05). ELISA results showed that, compared with group A, the expressions of VEGF, MMP13 and HIF1α in the serum of other groups were significantly increased (P < 0.05), among which, the expressions of VEGF, MMP13 and HIF1α were the highest in the serum of B mice, and the expressions of VEGF, MMP13 and HIF1α were all decreased in group C, D and E compared with group B (P < 0.05). Conclusion: WJTLT may play a role in relieving and treating knee osteoarthritis by regulating HIF1α and inhibiting the expression of VEGF and MMP13.
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