Doxazosin attenuates renal matrix remodeling mediated by anti-alpha(1)-adrenergic receptor antibody in a rat model of diabetes mellitus

摘要

Diabetic nephropathy is a major complication of diabetes mellitus (DM). Repent studies suggest that immunological mechanisms have a key role in the pathogenesis of DM, therefore these mechanisms may be important targets for diabetes therapy. The present study evaldated the effects of anti-aradrenergic receptor antibody (alpha(1)-R Ab) mediation and doxazosin treatment in a rat model of DM. It was observed that levels of 24-h urinary protein, serum creatinine and transforming growth factor-beta(1), in DM were significantly increased after alpha(1)-R Ab mediation (all P<0.05). In addition, electron microscopy identified severe damage in the renal tissue microstructures of DM rats following alpha(1)-R Ab mediation, while only mild abnormalities were observed in that of healthy rats mediated with alpha(1)-R Ab and of untreated DM rats. No marked abnormalities were observed in the renal tissue of healthy blank controls. Furthermore, in DM rats treated with alpha(1)-R Ab mediation + doxazosin intervention, the expression of TGF-beta(1) significantly decreased, and renal functions and renal matrix remodeling were significantly improved, relative to untreated DM controls (P<0.01). These results suggest that alpha(1)-R Ab may be involved in renal matrix remodeling during DM, and that kidney protection during DM may be achieved through treatment with corresponding receptor antagonists.