目的 研究氨基葡萄糖硫酸鹽對(duì)兔骨關(guān)節(jié)炎的保護(hù)作用，并探討其作用機(jī)制。方法 大耳成年家兔分為對(duì)照組、模型組、硫酸氨基葡萄糖膠囊（250 mg/kg）組和氨基葡萄糖硫酸鹽63、125、250 mg/kg組，每組8只。右膝Hulth手術(shù)方法建立骨關(guān)節(jié)炎模型。術(shù)后第1天開始給藥，各給藥組的給藥體積均為5 mL/kg，對(duì)照組給予等容量雙蒸水，1次/d，連續(xù)40 d，每天驅(qū)趕動(dòng)物行走0.5～1.0 h。觀察動(dòng)物體質(zhì)量變化，計(jì)算關(guān)節(jié)活動(dòng)度。肉眼和手術(shù)顯微鏡下進(jìn)行膝關(guān)節(jié)腔大體觀察；HE和甲苯胺藍(lán)染色，光鏡下觀察軟骨組織結(jié)構(gòu)、細(xì)胞數(shù)量、甲苯胺藍(lán)染色和潮線完整性，并按Mankin's評(píng)分標(biāo)準(zhǔn)對(duì)其退變程度進(jìn)行評(píng)分?；そM織常規(guī)制片和HE染色，光鏡下觀察其病理學(xué)改變并評(píng)分。鄰苯三酚法測(cè)定兔紅細(xì)胞中SOD活性。結(jié)果 與給藥前比較，氨基葡萄糖硫酸鹽各劑量組體質(zhì)量變化均有不同程度的增加，但差異均無統(tǒng)計(jì)學(xué)意義。與模型組比較，氨基葡萄糖硫酸鹽各劑量關(guān)節(jié)活動(dòng)度均有不同程度的增加，尤以氨基葡萄糖硫酸鹽250 mg/kg組明顯（P<0.05）。與模型組比較，氨基葡萄糖硫酸鹽各劑量組關(guān)節(jié)炎軟骨大體評(píng)分均明顯降低（P<0.01），表現(xiàn)為一定的量效關(guān)系。氨基葡萄糖硫酸鹽各劑量組的Mankin's評(píng)分的組織結(jié)構(gòu)、細(xì)胞數(shù)量、基質(zhì)染色和潮線完整性評(píng)分均有一定程度的好轉(zhuǎn)（P<0.05、0.01）。與模型組比較，氨基葡萄糖硫酸鹽不同劑量組能不同程度地降低滑膜評(píng)分，尤以氨基葡萄糖硫酸鹽125、250 mg/kg組作用明顯（P<0.05、0.01）。與模型組比較，氨基葡萄糖硫酸鹽各劑量組均能不同程度提高兔紅細(xì)胞中SOD活性，尤以氨基葡萄糖硫酸鹽250 mg/kg組作用明顯（P<0.05）。結(jié)論 氨基葡萄糖硫酸鹽對(duì)兔骨關(guān)節(jié)炎具有明顯的保護(hù)作用，且存在劑量相關(guān)性，其作用機(jī)制與減輕滑膜慢性炎癥反應(yīng)，提高紅細(xì)胞SOD活性有關(guān)。

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.

陜西省科技廳項(xiàng)目（2012sp2-08）