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目的 探讨马钱子总碱对兔膝骨Hulth-Telhag关节炎模型的作用及机制.方法 新西兰兔随机分为正常对照组,模型组,假手术组,马钱子总碱高、中、低剂量组,玻璃酸钠组,每组8只.除正常对照组外,其余各组均以Hulth-Telhag方法造模.造模8周后,马钱子总碱高、中、低剂量组分别给予兔每个膝关节腔注射0.3、0.2、0.1mL马钱子总碱注射液,玻璃酸钠组给予兔每个膝关节腔注射0.2mL玻璃酸钠,每周2次,连续用药5周.正常对照组、模型组及假手术组常规饲养,无其他特殊处理.停药1周后光镜观察关节软骨病理改变和Mankin′s评分,血液流变仪检测全血黏度(低切、中切、高切)及血浆黏度,ELISA检测关节液NO、SOD、过氧化脂质(LPO)及尿液吡啶酚(PYD)含量.结果 与正常对照组比较,模型组Mankin′s评分、全血黏度、血浆黏度、NO、LPO及PYD升高(P＜0.05),SOD降低(P＜0.05).与模型组比较,马钱子总碱高、中剂量组及玻璃酸钠组Mankin′s评分降低(P＜0.05);各给药组全血黏度、血浆黏度、NO、LPO及PYD降低(P＜0.05),SOD升高(P＜0.05).马钱子总碱中剂量组较低剂量组中、高切变率全血黏度、SOD升高(P＜0.05),NO、LPO及PYD降低(P＜0.05);马钱子总碱高剂量组较中剂量组全血黏度、血浆黏度升高(P＜0.05),NO、LPO及PYD降低(P＜0.05),SOD升高(P＜0.05).与玻璃酸钠组比较,马钱子总碱低剂量组Mankin′s评分、NO、LPO及PYD升高(P＜0.05),SOD降低(P＜0.05);马钱子总碱中剂量组Mankin′s评分、SOD降低(P＜0.05),NO、LPO及PYD升高(P＜0.05);马钱子总碱高剂量组Mankin′s评分、全血黏度及血浆黏度升高(P＜0.05).结论马钱子总碱对骨关节炎的软骨损伤具有修复作用,其机制主要与通过SOD途径抑制NO介导的软骨细胞凋亡有关,还与改善软骨代谢有关.“,”Objective To investigate the effect and mechanism of total alkaloids fromsemen strychni (TASS) in rabbit Hulth-Telhag model of knee osteoarthritis (OA) .Methods New Zealand rabbits were randomly divided into the normal control group, model group, sham operation group, high, medium and low dose TASS groups, and the sodium hyaluronate group, 8 in each group.With the exception of the normal control group, all groups received the Hulth-Telhag surgical procedure on knees to induce OA.Eight weeks after osteoarthritis modeling, high, medium and low dose TASS groups were administered with 0.3, 0.2, or 0.1 mL TASS injection into each joint cavity, respectively.In the sodium hyaluronate group, 0.2 mL of sodium hyaluronate was injected into each joint cavity.The treatment was given 2 times per week, for 5 consecutive weeks.New Zealand rabbits in the normal control group, model group, and sham operation group were conventionally fed, without other special treatment.One week after intervention, pathological changes of articular cartilage and Mankin′s score were observed by light microscopy.Hemorheology was used to detect whole blood viscosity (low shear, middle shear, high shear) and plasma viscosity.The levels of NO, SOD, and lipid peroxidase (LPO) in joint fluid and pyridol (PYD) in urine were measured by ELISA.Results Compared with the normal control group, the Mankin′s score of cartilage, whole-blood viscosity and plasmatic viscosity, the levels of NO, LPO and PYD were increased in the model group (P＜0.05) , while the SOD was decreased (P＜0.05) .Compared with the model group, the Mankin′s score of cartilage was decreased in the high and low dose TASS groups and sodium hyaluronate group (P＜0.05) ;whole-blood viscosity and plasmatic viscosity, the levels of NO, LPO and PYD in the synovial fluid decreased while the SOD was increased in the treatment groups (P＜0.05) .Compared with low dose TASS group, the medium dose TASS group exhibited an increased whole-blood viscosity and SOD levels (P＜0.05) , decreased synovial fluid levels of NO, LPO and PYD (P＜0.05) .Compared with medium dose TASS group, whole-blood and plasmatic viscosity, SOD levels were increased (P＜0.05) , NO, LPO and PYD levels in the synovial fluid were decreased in high dose TASS group (P＜0.05) .Compared with the sodium hyaluronate group, the Mankin′s score, NO, LPO and PYD levels were increased in the low dose TASS group (P＜0.05) , and SOD decreased (P＜0.05) ;the medium dose TASS group demonstrated decreased Mankin′s score and SOD (P＜0.05) , increased NO, LPO and PYD (P＜0.05) ;the high dose TASS group exhibited increased Mankin′s score, whole-blood viscosity and plasmatic viscosity (P＜0.05) .Conclusions The TASS treatment has a repairing function for cartilage injury in a model of osteoarthritis.The mechanism is likely related to inhibition of NO-mediated apoptosis of chondrocytes by the SOD pathway.Repair may also be mediated by the improvement of cartilage metabolism.