Zishenwan Decreases Kidney Damage in Recurrent Urinary Tract Infection through the Inhibition of Toll-Like Receptor 4 Signal

OBJECTIVES: To investigate the mechanism of the protective effect of Zishenwan on pyelonephritis rats. METHODS: In the rat model of pyelonephritis, protective effects of Zishenwan, the content of secretory immunoglobulin A (SIg A), and interleukins were detected by ELISA. The expressions of TLR4-NFκB pathway were detected by Western blot in renal and urinary tract mucosa. The protective effect and influence on TLR4-NFκB pathway of Zishenwan were studied. RESULTS: Zishenwan protected rats from pyelonephritis which related to the increase of SIgA, the regulation of interleukins, and the inhibition of TLR4-NFκB pathway. Serum containing Zishenwan can significantly decrease LPS-induced expression of TLR4, MyD88, and NFκB in vitro. And the inhibition of TLR4 signal by Zishenwan related to the degradation of TRAF3 and TRAF6. CONCLUSIONS: Zishenwan protected rats from urinary tract infection by clearance of bacteria and decrease of tissue damage. 20S proteasomes mediated the degradation of TRAF3 which is important to the decrease of tissue damage from Zishenwan.