Effect Of Carboxymethylated Chitosan On PG,NO,iNOS And MMP－1 Of Cartilage Of Rabbit Osteoarthritis

Osteoarthritis(OA) is a common chronic articular cartilage degenerative disease in elderly. It severely impairs healthy and life quality of the elderly. Fundamental pathologic change of OA is articular cartilage degeneration. Although the mechanism of OA is remained obscure and there is no effective therapy presently, people has realized that OA is a chronic disease with cartilage degenerative changes characterized by metabolism mess and decline of articular cartilage. The cartilage has no blood to carry. Once there are injuries which cause cartilage degenerative changes, cartilage lack oneself rebirth repair ability. So only we research to manufacture drugs which can promote repairs of cartilage and rebuild structure of bone, can we resolve the treatment of OA radically. Lots of researches expressed that chitin and its derivatives chitosans have ability of action as carriers of cartilage cell growth and promoting cartilage repairs, but they are not used for OA prevention and cure. Owing to this, Chemical collage of WuHan university and us research to manufacture a kind of new chitosans derivatives with higher deliquescent and organize compatibility: high deacetylating of carboxymethychitosan(HD-CMC). In this study , we observed the effects of the high deacetylating of carboxymethychitosan intra-articular given on cartilage degradation of rabbit OA induced anterior cruciate ligament transaction(ACLT).Objective: Using experimental rabbit unilateral ACLT model of OA to observe the effects of the high deacetylating of carboxymethychitosan , intra-articular given, on cartilage degradation.Methods: OA was induced in 36 rabbits by ACLT. Randomly selected 18 rabbits as experimental group and gave them intra-articular injection of 0.3ml of 2% HD-CMC at once after operation, once two weeks. Other 18 rabbits of control group received intra-articular injection of 0.3ml normal saline at the same time respectively . Randomly selected 9 rabbits in each group and killed them at the 6th week. The left 18 rabbits were killed at the 12^th week, changes in macroscopic and pathologic of Cartilage of femoral condyles of two groups rabbits were contrasted to each other, the content of nitricoxide( NO) in joint liquid and glycosaminoglycans(GAG) in cartilage of one group was compaired with another one. the changes of mRNA and protein expression levels of matrix metalloproteinase-l(MMP-l) and inducible nitric oxide synthase(iNOS) between two groups were detected by RT-PCR and ImmunohistochemistryResults: Cartilage degradation in control group was significantly more severe than that in experimental group in macroscopic grading scale and in the microscopic change. The detection of proteoglycan showed that the quantity of GAG were increased in experimental group than that in control group. The content of NO in joint liquid in experimental group were significant lower than that in control group. mRNA and protein expression levels of MMP-1 and iNOS were all declined in experimental group than that in control group.Conclusion: It is suggested that the HD-CMC might reduce the severity of cartilage degaradation and not only improve the synthesization but also decline mRNA and protein expression levels of MMP-1 and iNOS. So we think the high deacetylating of carboxymethychitosan would be a potential drug for the treatment of OA and is worthy of studying more.