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目的观察牛膝总皂苷(TSA)对兔膝骨关节炎(KOA)软骨组织形态变化及关节液中细胞因子白细胞介素1β(IL-1β)和转化生长因子β1(TGF-β1)含量的影响。方法将36只新西兰兔,随机分为空白对照组,模型组,阳性对照组(硫酸氨基葡萄糖,60 mg·kg~(-1)),牛膝总皂苷高、中、低(200,100,50 mg·kg~(-1))剂量组。采用改良Hulth法复制兔膝骨关节炎模型。药物干预2个月后,采用ELISA法检测各组兔膝关节液中IL-1β、TGF-β1的水平,分别于光镜及透射电镜下观察各组兔关节软骨的组织形态学变化。结果与空白对照组比较,模型组兔膝关节液中IL-1β的含量明显增高(P<0.01),TGF-β1的含量明显降低(P<0.01);与模型组比较,各给药组IL-1β的含量明显降低(P<0.01),TGF-β1的含量显著增高(P<0.01)。光镜下观察关节软骨组织形态变化,结果表明TSA呈剂量依赖的抑制了软骨组织的退变。各组兔KOA软骨组织结构Mankin评分结果表明,与空白对照组比较,模型组评分明显增加(P<0.01);与模型组比较,各给药组评分明显减少(P<0.05,P<0.01)。透射电镜下观察关节软骨细胞形态学变化,结果表明TSA具有呈剂量依赖的保护软骨细胞的作用。结论 TSA能抑制细胞因子IL-1β的表达,提高转化生长因子TGF-β1的表达,具有保护软骨组织缓解软骨退变的作用。
Objective To observe the changes of cartilage histomorphology of knee osteoarthritis (KOA) and the content of cytokines IL-1β and TGF-β1 in synovial fluid of rabbits with TSA (TSA) . Methods Thirty-six New Zealand white rabbits were randomly divided into blank control group, model group, positive control group (glucosamine sulfate 60 mg · kg -1), high, medium and low (200, 100, 50 mg · Kg ~ (-1)) dose group. Rabbit knee osteoarthritis model was reproduced by modified Hulth method. After intervention for 2 months, the levels of IL-1β and TGF-β1 in knee joint fluid of rabbits in each group were measured by ELISA. The histomorphology of articular cartilage of rabbits in each group were observed under light microscope and transmission electron microscope. Results Compared with the blank control group, the content of IL-1β in the knee joint fluid of the model group was significantly increased (P <0.01) and the content of TGF-β1 was significantly decreased (P <0.01). Compared with the model group, (P <0.01), while the content of TGF-β1 was significantly increased (P <0.01). The morphological changes of articular cartilage were observed under light microscope. The results showed that TSA inhibited the degeneration of cartilage tissue in a dose-dependent manner. Mankin score of KOA cartilage in each group showed that compared with the blank control group, the score of the model group increased significantly (P <0.01); Compared with the model group, the score of each group decreased significantly (P <0.05, P <0.01) . The morphological changes of articular chondrocytes were observed under transmission electron microscope. The results showed that TSA had a dose-dependent protective effect on chondrocytes. Conclusion TSA can inhibit the expression of cytokine IL-1β, increase the expression of transforming growth factor-β1 and protect cartilage tissue from cartilage degeneration.