Protective effects of Cyclopamine in adjuvant arthritis rats kidney injury and mechanism research / 中国免疫学杂志

ABSTRACT

Objective:Observed activity of adjuvant arthritis ( AA) rats Hedgehog signaling pathway and explore the effect of Cyclopamine on rat arthritis and kidney injury.Methods:40 rats were randomly divided into control group,Cyclopamine group,AA+Cyclopamine group and AA model group.We used Freund′s complete adjuvant rat model with Cyclopamine intraperitoneal injection.By measuring paw swelling, systemic inflammation and arthritis semi-quantitative assessment methods of rats to evaluate the model.HE staining was used to detect the renal pathological changes of rats.Western blot was used to detect kidney Gli1 protein expression levels of the rats.Immunohistochemical staining was used to detect the rat kidney TNF-α,IFN-γ,IL-6 expression.Results:After using Cyclo-pamine,the AA rat paw swelling reduced and arthritis refers relieved significantly.Compared with the control group,Cr,BUN and organ coefficient increased significantly in AA model group, and the difference was statistically significant.Meanwhile renal TEM detection appeared obvious pathological changes in rats of AA model group.After using cyclopamine,the content of Cr,BUN and organ coefficient change reduced significantly, so did the pathological.Western blot detected kidney tissue Gli1 protein in each group.Compared to control group,there was no significant difference in Cyclopamine group.AA model group and AA+Cyclopamine group Gli1 protein expression was significantly higher compared with Cyclopamine Gli1 protein group,the difference was statistically significant.AA model group and AA Cyclopamine group Gli1 protein expression was significantly higher,the difference was statistically significant.Compared to the AA model group,AA+Cyclopamine group Gli1 protein levels have decreased significantly,the difference was statistically signifi-cant.Immunohistochemical assay detection found that kidney tissue proinflammatory cytokines TNF-α,IFN-γ,IL-6 expression and semi-quantitative score changed.Compared with the control group, TNF-α, IFN-γexpression of AA model group were significantly increased.After using Cyclopamine,the expression of TNF-α,IFN-γin kidney of AA model reduced significantly.IL-6 expression in AA model group was significantly higher than the control group.Conclusion:Cyclopamine AA can relieve arthritis and kidney injury in rats with arthritis AA,the Hh pathway was on activity state in the process,may altered expression of inflammatory factors.