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[摘要]
目的 研究氨基葡萄糖硫酸盐对兔骨关节炎的保护作用,并探讨其作用机制。方法 大耳成年家兔分为对照组、模型组、硫酸氨基葡萄糖胶囊(250 mg/kg)组和氨基葡萄糖硫酸盐63、125、250 mg/kg组,每组8只。右膝Hulth手术方法建立骨关节炎模型。术后第1天开始给药,各给药组的给药体积均为5 mL/kg,对照组给予等容量双蒸水,1次/d,连续40 d,每天驱赶动物行走0.5~1.0 h。观察动物体质量变化,计算关节活动度。肉眼和手术显微镜下进行膝关节腔大体观察;HE和甲苯胺蓝染色,光镜下观察软骨组织结构、细胞数量、甲苯胺蓝染色和潮线完整性,并按Mankin's评分标准对其退变程度进行评分。滑膜组织常规制片和HE染色,光镜下观察其病理学改变并评分。邻苯三酚法测定兔红细胞中SOD活性。结果 与给药前比较,氨基葡萄糖硫酸盐各剂量组体质量变化均有不同程度的增加,但差异均无统计学意义。与模型组比较,氨基葡萄糖硫酸盐各剂量关节活动度均有不同程度的增加,尤以氨基葡萄糖硫酸盐250 mg/kg组明显(P<0.05)。与模型组比较,氨基葡萄糖硫酸盐各剂量组关节炎软骨大体评分均明显降低(P<0.01),表现为一定的量效关系。氨基葡萄糖硫酸盐各剂量组的Mankin's评分的组织结构、细胞数量、基质染色和潮线完整性评分均有一定程度的好转(P<0.05、0.01)。与模型组比较,氨基葡萄糖硫酸盐不同剂量组能不同程度地降低滑膜评分,尤以氨基葡萄糖硫酸盐125、250 mg/kg组作用明显(P<0.05、0.01)。与模型组比较,氨基葡萄糖硫酸盐各剂量组均能不同程度提高兔红细胞中SOD活性,尤以氨基葡萄糖硫酸盐250 mg/kg组作用明显(P<0.05)。结论 氨基葡萄糖硫酸盐对兔骨关节炎具有明显的保护作用,且存在剂量相关性,其作用机制与减轻滑膜慢性炎症反应,提高红细胞SOD活性有关。
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[Abstract]
Objective To study protective effects of glucosamine sulphate against knee osteoarthritis in rabbit and explore its mechanism. Methods Rabbits were randomly divided into control group, model group, and glucosamine sulphate (63, 125, and 250 mg/kg) groups, and each group had eight rabbits. Right knee Hulth procedure was used to establish osteoarthritis models. The volume was 5 mL/kg, the treatment were carried out once daily, and lasted for 40 d. Body weight changes were observed, and joint mobility in rabbits were calculated. Gross tissue of rabbits with osteoarthritis was observed under naked eye and microscope. Cartilage tissue structure, cell number, toluidine blue staining, and the tidal line integrity were observed after He and toluidine blue staining, and Mankin's scores were compared. Pathological changes of synovial tissue and scores were compared. SOD activity in red blood cells of rabbits was determined by pyrogallol method. Results Compare with treatment before giving medicine, body weight changes in glucosamine sulphate group were increased, but the difference was not statistically significant. Compare with model group, joint mobility of rabbits in the glucosamine sulphate groups were significantly increased, especially glucosamine sulphate 250 mg/kg group (P<0.05); The gross score of arthritis cartilage were significantly decreased with a certain dose-effect relationship (P<0.01); Cartilage tissue structure, cell number, toluidine blue staining, and the tidal line integrity in Mankin's scores had a certain degree of improvement (P<0.05, 0.01); Synovial tissue scores were significantly decreased, especially glucosamine sulphate 125 and 250 mg/kg group (P<0.05, 0.01); And SOD activity in red blood cells were significantly increased, especially glucosamine sulphate 250 mg/kg group (P<0.05). Conclusion Glucosamine sulphate has protection against knee osteoarthritis in rabbit in dose-dependent manner,which may be related to reducing chronic inflammation of synovial membrane, and improvement of SOD activity in red blood cells.
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[基金项目]
陕西省科技厅项目(2012sp2-08)