Mechanism of Aminoguanidine Regulating Oxidative Stress and Transforming Growth Factor-β Pathway Mediated Renal Fibrosis in Diabetes Rats

GUO Jianying; LI Tong; HU Haofei; LIAO Ying

doi:10.16458/j.cnki.1007-0893.2024.24.002

Abstract：Objective To explore the mechanism of aminoguanidine(AG)affecting renal fibrosis in diabetes rats via regulating oxidative stress mediated by transforming growth factor-β(TGF-β)pathway.Methods Twenty four male Sprague-Dawley rats aged 6 to 7 weeks were randomly divided into normal control(NC)group,diabetes model(DN)group,and DN+AG group,with 8 rats in each group.The blood urea nitrogen(BUN),serum creatinine(Scr),and 24h urinary protein concentration in each group of rats were measured.The levels of total antioxidant capacity(T-AOC),superoxide dismutase(SOD),lipid peroxidation(LPO),malondialdehyde(MDA),hydroxyproline(Hyp),and TGF-β1 messenger ribonucleic acid(mRNA)expression in the kidney tissues of each group of rats were measured.The expression levels of nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase-1(HO-1),quinone oxidoreductase 1(NQO1),TGF-β1,maternal anti limb paralysis homolog 3(Smad3),and type Ⅳ collagen Ⅳ(Collagen-Ⅳ)protein were detected by enzyme linked immunosorbent assay(ELISA)method.Results Compared with NC group,The levels of BUN,24h urinary protein concentration,Scr,LPO,MDA,Hyp,TGF-β1 mRNA,TGF-β1,Smad3 and Collagen-Ⅳ in DN and DN+AG groups were significantly increased.The levels of T-AOC,SOD,Nrf2,HO-1 and NQO1 were significantly decreased.Among them,the levels of BUN,24h urinary protein concentration,Scr,LPO,MDA,Hyp,TGF-β1 mRNA,TGF-β1,Smad3 and Collagen-Ⅳ of DN+AG group were significantly lower than those of DN group,while the levels of T-AOC,SOD,Nrf2,HO-1 and NQO1 were significantly higher than those of DN group.And the above differences were statistically significant(P<0.05).Conclusion AG can alleviate renal fibrosis in diabetic rats and show renal protection.The beneficial effect of AG on renal injury may be realized by activating Nrf2/HO-1/NQO1 pathway to inhibit oxidative stress and down-regulating TGF-β1/Smad3 pathway to regulate Collagen-Ⅳ protein expression.