Experimental Study On The Treatment Of Osteoarthritis With Simvastatin

Objective:To study the effect of Simvastatin on histology in cartilage of rabbit osteoarthritis model. Method:Thirty New-Zealand Rabbits were randomly divided into 5 groups:Group A,B,C,D,E. The OA model was established in group B,C,D,E by Hulth Method. Group A was normal control and received nothing.Group B was received intraarticular injection with sterilized normal saline.Group C,group D and group E were received intraarticular injection with different dose of simvastatin. All rabbits were killed 6 weeks postoperation,the knee joints were assessed by morphological method; and then, cartilage tissue were obtained and sections were made and stained with HE/SOFG for Mankin score. Result:Cartilage impairment in group B was more serious than other group.Mankin score in group A,C,D,E was lower than group B.Conclusion:OA model was established successfully. Intraarticular injection with simvastatin can protect articular cartilage from impairment by promoting synthesis of proteoglycan. Objective:To observe the effect of Simvastatin on level of IL-1 in synovia and type II collagen in cartilage of osteoarthritis rabbits. Method:Thirty New-Zealand Rabbits were randomly divided into 5 groups:Group A,B,C,D,E. The OA model was established in group B,C,D,E by Hulth Method. Group A was normal control and received nothing.Group B was received intraarticular injection with sterilized normal saline.Group C,group D and group E were received intraarticular injection with different dose of simvastatin. All rabbits were killed 6 weeks postoperation. The expression of MMP-13 was detected by immunohistochemical method and reverse transcription-polymerase chain reaction (RT-PCR).Gene expression of typeⅡcollagen was detected by using RT-PCR. The level of IL-1 in synovia was deteccted by ELISA method. Result:The expression of mmp-13 mRNA was significantly decreased in group C,D,E compared with group B.The expression of typeⅡcollagen was significantly increased in group C,D,E compared with group B.Conclusion:Intra-articular administration of Simvastatin can lower the level of MMP-13 and IL-1 and upregulate expression of typeⅡcollagen,thus limiting cartilage degradation. Objective:To observe the effect of Simvastatin on apoptosis of cartilage of osteoarthritis rabbits. Method:Thirty New-Zealand Rabbits were randomly divided into 5 groups:Group A,B,C,D,E. The OA model was established in group B,C,D,E by Hulth Method. Group A was normal control and received nothing.Group B was received intraarticular injection with sterilized normal saline.Group C,group D and group E were received intraarticular injection with different dose of simvastatin. All rabbits were killed 6 weeks postoperation. Cartilage tissue were obtained, chondrocyte apoptosis was detected by flow cytometry. The expression of Bcl-2 mRNA was detected by RT-PCR Result:The expression of BCL-2 mRNA was significantly decreased in group A,C,D,E compared with group B.The ratio of apoptotic cells was significantly increased in group D,E compared with group B.Conclusion:Intra-articular administration of Simvastatin can lower the ratio of chondrocyte apoptosis by downregulating expression of BCL-2 mRNA. Objective:to study the effect of hyaluronic acid (HA) on chondrocyte apoptosis in a rat osteoarthritis in vitro model and explore its mechanism. Method:Primary rabbit chondrocytes were cultured and induced to apoptosis by 10ng/ml interleukin-1β(IL-1β).After treatment with various concentrations of Simvastatin(10,50,100umol/l), the apoptotic rate, mitochondrial function, nitric oxide production, and the levels of inducible nitric oxide synthase (iNOS) mRNA in IL-1β-induced chondrocytes were examined. Results:Simvastatin could inhibit chondrocyte apoptosis in a dose-dependent manner. Furthermore, it could partly restore the levels of mitochondrial membrane potential, decrease nitric oxide production by down-regulation of iNOS mRNA expression in chondrocytes induced by IL-1β. Conclusion:The inhibitory effects of Simvastatin on IL-1β-induced chondrocyte apoptosis were possibly due to the protection of mitochondrial function, the decline in the levels of nitric oxide.