J24924 possesses cardiovascular and renal protective effects on pristane-induced lupus through inhibition of RhoA/Rho kinase pathway in mice

摘要

OBJECTIVE To explore whether J24924could prevent the development of pristane-induced lupus in a mouse model,and whether it could protect renal and lower the cardiovascular risk.METHODS The effect of J24924 was assessed in female BALB/c mice intraperitoneal injected with 0.5 m L of pristane,and serum autoantibodies were tested every month,blood pressure wasmeasured every 2 months,while serum inflammatory markers,spleen pathologic characteristics,renal injury and vascular function were observed at 6 month.RESULTS J24924 could decrease serum autoantibodies and serum inflammatory markers in the SLE mice and improved the spleen pathologic characteristics,and at the same time improved the renal injury and decreased inflammatory responses in kidneys,reduced blood pressure and improved vascular endothelial function.Western blotting assays revealed that inhibition for the activation of NF-κB and Rho/ROCKs signaling pathways and the downstream signaling molecules might be the potential mechanisms of J24924.CONCLUSION Our findings suggestthat therapy of J24924 may be a strategy to prevent SLE and ameliorate associated kidney and cardiovascular complications.