| Objective:To explore the correlation among melatonin,calmodulin and osteoarthritis.Methods:In this experiment,40 healthy 6-month-old SD male rats weighing 200-250 g were used to construct a knee osteoarthritis model by injecting papain into the knee joint cavity.After verifying the successful modeling by use of magnetic resonance imaging,they were randomly divided into 4 groups of A,B,C,and D,of which: model control group(group A),melatonin antagonist(Luzindole)group(group B),calmodulin antagonist(tamoxifen)group(Group C),melatonin antagonist(Luzindole)+ calmodulin antagonist(Tamoxifen)group(Group D).After the modeling was completed,rats were adaptively fed for 1 week,and group A was injected intraperitoneally with saline 1ml / kg / d for 4 weeks.Group B was intraperitoneally injected with 0.2 mg / kg / d luzindole solution for 4 weeks.Group C was injected intraperitoneally with TMX 0.2mg/kg/d for 4 weeks.Group D was injected intraperitoneally with luzindole solution 0.2mg / kg / d + TMX 0.2mg / kg for 4 weeks.Serum was obtained by collecting tail blood of rats before and at the 2nd and 4th weeks after the administration.Enzyme-linked immunosorbent assay was used to detect changes in IL-1β,IL-6,COX-2 and calmodulin content.Finally,all rats were sacrificed.Pathological sections were taken from the right knee joint of each group and the left knee joint of group A rats,and HE staining and toluidine blue staining were performed.The pathological changes under the microscope were observed and the Mankin score was performed.Results:There was no significant difference in the changes of various indicators after modeling in group A(p> 0.05).The levels of IL-1β,COX-2,and IL-6 in the remaining groups gradually increased with the progress of the experiment and reached the highest in the fourth week..At the 2nd and 4th week,the levels of inflammatory factors in each group were higher than those in group A,and the differences were statistically significant(p <0.05).The level of inflammatory factors in group D was the highest,and the differences were statistically significant(p <0.05),suggesting that the degree of osteoarthritis was the highest in group D and the lightest in group A.There was no significant difference between groups B and C(p> 0.05).The calmodulin index in groups C and D gradually decreased with the progress of the experiment,and it was statistically significant compared with the other groups(p <0.05),but there was no significant difference between the two groups(p> 0.05).At the same time,we observed a progressive increase in calmodulin levels in group B rats,which was significantly different from that in group A(p <0.05).The Manlin’s scores of the right knee joint pathological sections in each group were significantly different between the groups(P <0.05).The structure of the articular cartilage was unclear,some of the cartilage showed vertical or horizontal matrix ciliated tears,and even cartilage tear Detachment,separation of the tide line,breakage,and reduced staining of cartilage matrix.The degree of osteoarthritis of the left knee joint in each group was significantly more severe than that in group A,and was statistically significant(P<0.05).The score of group D was higher than that of groups A,B and C,and group A was the lightest.Conclusions:In the experimental rats,inhibiting the levels of melatonin and calmodulin separately or simultaneously can aggravate osteoarthritis of the knee joints of rats.This suggests that the atients who arev using tamoxifen may cause an increased incidence of osteoarthritis. |
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