Xiaokeping Mixture Attenuates Diabetic Kidney Disease by Modulating TGF-β/Smad Pathway in db/db Mice

Abstract

Xiaokeping mixture (XKP), a traditional Chinese medicine compound preparation, has achieved widespread use for diabetes mellitus and its kidney damage in clinical practice. The current study was carried out to assess the protective effect of XKP in spontaneous diabetic db/db mice and the underlying mechanism whereby XKP regulates TGF-β/Smad pathway. Male C57BLKS/J db/db mice, 12 weeks old, were randomly divided into 3 groups: the model group, 17.5 mg/kg irbesartan-treated group (IST group), and 8 g/kg XKP-treated group (XKP group), while age-matched db/m mice were selected as a control group. After 8 weeks of administration, serum and urea samples were collected from mice for biochemical tests, while the kidneys were removed for histological analysis. The expression of TGF-β/Smad pathway-related mRNA and protein were measured by RT-PCR and western blot analysis. Treatment with XKP significantly improved renal function and attenuated the pathological change of diabetic kidney disease (DKD) in renal histopathology. Furthermore, the overexpression of TGF-β1, Smad3, and p-Smad3 was inhibited, as well as the reduction of Smad7 and SIP1 was weakened by XKP. In conclusion, these results suggest that XKP could attenuate DKD by modulating TGF-β/Smad pathway.