| Objectives: To researth the mechanisms of intraarticular injecting Acanthopanax senticosus treating idiopathetic osteoarthritis of the knee joint.Methods: 64 New Zealand white rabbits were banlenced divided into 4 groups (n = 16), 16 Nonsurgical rabbits as a normal group, and the remaining 48 with resection of the partial medial meniscus model, subsequently divided into model group, Acanthopanax senticosus group and sodium hyaluronate group, the model group and the normal group were given no treatment. Each animal of Acanthopanax senticosus group was injected 0.5ml Acanthopanax senticosus parenteralia into the operative side knee weekly. The sodium hyaluronate group was given 0.3ml HA in the same way. All regimens were executed at 2 weeks after operation until 1 week before the animal sacrificed. At 6 weeks and 10 weeks both time points, all rabbits' serum and synovial fluid was collected, then all samples of NO, iNOs, SOD and MDA levels were tested. At the same time point animals were killed, the surface of articular , synovial membrane, osteophyte size and cartilage ulcer area were estimated. In order to observe the situation of subchondral bone sclerosis and joint space, knee X-ray photo were taken. Cartilage and synovial membrane paraffin sections were made and stained with H&E and AB-PAS, respectively. By light microscope, each section was evaluated and scored. Chondrocyte apoptosis were detected by in situ terminal labeling method, the expression of bcl-2 in cartilage and urokinase-type plasminogen activators (uPA) in synovial membrane were detectived by immunohistochemistry technique.Results: At both time points, the normal group has shiny smooth articular surface, with transparent cartilage appearence, no obvious defects and osteophyte generating, as well as synovial congestive. At 6 week, there were more severe changes in model group than other group.At 10 week; there was a rough matte articular surface, markedly opaque defective cartilage, a lot of new biology formation, dark swelling congesting synovium in model group. While, Acanthopanax senticosus group has a less rough articular surface, a light gloomy cartilage, more superficial ulcers, lower degree of transparency, little to moderate amount of osteophyte formation and a light swelling synovium. Except for larger osteophyt formation in HA group than that in cwj group, there was no significant difference between the two groups. Over time, each of the rabbits' knee OA defect has aggravated, so it pathological score increased. Animals in each group, at the end of 6 week, there had been slight subchondral bone osteosclerosis and joint space narrow happened, and, at 10 week, all these got wores. Except for the normal group, H&E and AB-PAS staining showed that the integrity of cartilage was damaged to various degrees. The extent of AB-PAS staining losing indicated that the different proteoglycan decrease in the matrix of the cartilage among the three operation groups, As well as some new born veins and fibrosis were found in the articular cartilage sections. There was the most defective cartilage in model group. Also, with the time past, neovascularization and fibrosis formation were more and more severe. At the end of 6 week, when compared with the normal group, in all surgery groups, serum and synovial fluid values of NO increased significantly (P <0. 05). However, the level of No in Acanthopanax senticosus and HA group was changed slightly. (P> 0. 05) Although iNOs value of HA group and model group increased significantly (P<0. 05), there was no significant changes in Acanthopanax senticosus group (P>0. 05). HA group had higher iNos values than that of Acanthopanax senticosus Group (P<0. 05). compared to normal group, those three surgery group have significantly lower SOD levels, but higher MDA levels (P<0. 05). At 10 weeks, in all three surgical groups, serum and synovial fluid of the NO, iNos, MDA levels were higher than that in the normal group (P <0. 05), in addition, the model group had the highest values. There was significantly lower NO levels in Acanthopanax senticosus group than that in HA group (P <0. 05). SOD levels of three surgery groups were lower than that of the normal group(P<0. 05). Also, compared to the HA group, Acanthopanax senticosus group had higher SOD level (P <0. 05). It seems that the levels of MDA and iNOS in HA group was slightly higher than that of in the Acanthopanax senticosus group, but, it was no statistical significance, compared to the end of 6 weeks, at the end of 10 weeks, the NO, iNOS and MDA level of the serum and synovial fluid of the joints appeared upward tendency (P<0. 05), however, SOD levels was declined markedly (P<0. 05). Both of those two time points, the index of apoptosis of the HA and Acanthopanax senticosus group were lower than that of the model group (P<0. 05), but, bcl-2 expression was higher than that of the model group (P < 0. 05). There was no difference between Acanthopanax senticosus group and the HA group (p>0. 05). AT 6 weeks, positive expression of synovial uPA in the three surgery group was stronger than that of the normal group(P <0. 05), positive expression of synovial uPA in the HA and the Acanthopanax senticosus group were weaker than that of the model group (P < 0.05). By the 10 weeks, compared to 6 weeks, positive expression of uPA in HA Acanthopanax senticosus and normal groups had no significant changes .Although It seemed that there was an upward trend of positive upa expression in the model group, it was no difference statistically.Conclusions: The rabbit's experimental osteoarthritis disease progression can be slowed down by intraarticular injection of Acanthopanax senticosus. The mechanisms may be:1,Joint degeneration may be slowed by Acanthopanax senticosus by both mediators which is synovium and cartilage.2,By using Acanthopanax senticosus, blood circulation may be promoted to remove blood stasis,Synovial lesions may be improved. Because of its immunal stability and role of glucocorticoid-like, macrophage activation was inhibited, thus,iNOS expression , NO formation and uPA expression in the synovium could be reduced, as a result, the generation of inflammatory cytokines may be cut down, the apoptotic index could be reduceded, so, the cartilage lesions got lighted.3,Acanthopanax senticosus being an antioxidant, levels of SOD in both synovial fluid and blood could be elevated as well as bcl-2 expression in cartilage, however, the MDA levels could be lowered, subsequently, the cartilage cells could be prevented from oxidative stress damage, and apoptotic index of cartilage cells could be cut down. |
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