| Osteoarthritis (OA) is one of chronic degenerative joint diseases, which is especially harmful to the health of aged people. OA often occurs in knee joints. With the aging of social population, the incidence rate of OA is increasing. Nowadays, there are about 60 million to 70 million people suffer from this kind of diseases to some extent in our country.Chondroitin sulfate is an important component of articular cartilage. CS possesses various pharmacological actions and physiological functions, such as protecting cartilage, promoting the formation of cartilage matrix and relieving joint pain, etc. The protective effect of CS on articular cartilage was manifested in vitro and in vivo. CS can improve the symptoms of osteoarthritis in clinical application.Sodium hyaluronate (SH) is an important component of synovial fluid and articular cartilage with the extensive presence in polymorphic cartilage cells and synovial cells. SH plays an important role in lubrication, buffering and screening of joints and cartilage, as well as construction and repair of articular cartilage. SH injection into articular cavity has become the main method in treating OA, which can increase the viscoelasticity and lubricity of joint synovial fluid, improve the symptoms of OA, restore the viscoelasticity of synovial membrane and cartilage matrix, and reduce inflammation.The influence of CS on proliferation and collagen II synthesis of chondrocytes in vitro was examined. Effects and mechanisms of CS and SH (CS-SH) injection on OA in rabbits were also explored. The main results of this study are listed as follows.1. Influence of CS on proliferation and collagen II synthesis of chondrocytesIt was shown that CS could promote the synthesis of collagen type II and had no influence on proliferation of chondrocytes.2. Preparation of CS-SH injection CS-SH injection was prepared and stable and quality controllable preparation was obtained.3. Effect of CS-SH injection on OA in rabbitsEffects of CS-SH injection on knee OA in rabbits induced with papain were evaluated. The animals were randomized into for groups and treated with CS-SH injection, CS injection, SH injection or NS injection, respectively. After 5 weeks of treatment, the knee joints of animals were collected and histopathological evaluation was performed. It was shown that treatment with CS-SH injection could significantly improve the symptoms of OA which was assessed by Mankin grade. The effect of CS-SH injection was better than that of SH injection.4. Mechanism of CS-SH injection on OAThe content of glycosaminoglycans (GAG), which was extracted by alkaline hydrolysis and protease digestion from knee joint cartilage of OA in rabbits treated with injections was determined by azur A colorimetry method. The results indicated that the content of prostaglandin in cartilage of animals treated with CS-SH injection was greatly increased.The effects of CS-SH injection on the expression levels of IL-1β, TNF-αand TMP-1 in synovial fluid after treatment were assessed. It was shown that CS-SH injection could significantly inhibit the expression of IL-1βand TNF-αand enhance the expression of TIMP-1. The results also indicated that CS-SH injection could significantly inhibit the expression of NO and iNOS.The results indicate that CS-SH injection may exert therapeutic action on OA by the mechanisms including the protective effect of CS on chondrocytes and decreased expression of IL-1βand TNF-α, increased expression of TIMP-1, as well as decreased expression of NO and iNOS in synovial fluid after treatment with CS-SH injection, and the lessening of inflammation of knee joint thereafter.The main achievements and conclusions of this paper are as follows.(1) CS can promote the synthesis of collagen type II and has no influence on proliferation of chondrocytes.(2) Stable and quality controllable CS-SH injection was prepared. (3) CS-SH injection could protect articular cartilage, lessen inflammation and significantly improve OA symptoms.(4) The mechanisms of CS-SH on osteoarthritis may owing to the expression decrease of IL-1βand TNF-αand the expression enhancement of TIMP-1, as well as the expression decrease of NO and iNOS in synovial fluid of OA animals. Thus the the degradation of OA cartilage was inhibited. The effect of CS-SH injection was better than that of SH injection.
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