Journal of Shandong University (Health Sciences) ›› 2020, Vol. 58 ›› Issue (3): 75-80.doi: 10.6040/j.issn.1671-7554.0.2019.1510

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Daglixamine inhibits renal fibrosis in rats with diabetic nephropathy via Klotho/TGF-β1 signaling pathway

DING Hualin1, LI Yangyang2, YU Fengyuan1, ZHAN Weiwei1, YU Suguo1   

  1. 1. Department of Endocrinology;
    2. Department of Pathology, Affiliated Hospital of Binzhou Medical College, Binzhou 256603, Shandong, China
  • Online:2020-03-10 Published:2022-09-27

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Abstract: Objective To investigate the effect of daglicaten on renal fibrosis in rats with diabetes-related nephropathy(DN)and to explore the possible mechanism. Methods A total of 20 male SD rats were randomly divided into the normal control group, model group, metformin group and daglipetide group, with 5 rats in each group. After models were established, the rats were divided into different groups for intervention. The renal function indexes were detected after 12 weeks, including blood urea nitrogen(BUN), serum creatinine(Scr)and 24-hour urine protein(24 h UP). The morphological changes were observed with HE staining. The expressions of Klotho protein and transforming growth factor β1(TGF-β1)in serum and kidney tissues were detected with ELISA and immunohistochemistry. Results The model group had significantly higher BUN, Scr, and 24 h UP than the normal control group(P<0.01); the metformin group had significantly lower BUN, Scr, and 24 h UP than the model group(P<0.05); the dagalegrin group had lower BUN, Scr, and 24 h UP than the metformin group(P<0.05). The model group had worse renal tubular injury than the normal group(9.4±0.55 vs 2.8±1.00, P<0.01); the metformin group had less renal tubular injury than the model group 山 东 大 学 学 报 (医 学 版)58卷3期 -丁华琳,等.达格列净通过Klotho/TGF-β1通路抑制糖尿病肾病大鼠肾纤维化的作用 \=-(7.0±0.90 vs 9.4±0.55, P<0.05); the daglicaten group had less renal tubular injury than the metformin group(5.6±1.0 vs 7.0±0.90, P<0.05). The model group had lower Klotho protein but higher TGF-β1 levels than the normal control group; the metformin group had higher Klotho protein but lower TGF-β1 levels than the model group; the daglicaten group had higher Klotho protein but lower TGF-β1 levels than the metformin group; all differences were statistically significant(P<0.05). Conclusion Daglipine inhibits TGF-β1-mediated fibrosis signaling by up-regulating Klotho protein expression and thus attenuates renal fibrosis in rats with diabetes-related nephropathy.

Key words: Daglipine, Klotho protein, Transforming growth factor β1, Diabetic nephropathy, Fibrosis signal transduction, SD rats

CLC Number: 

  • R587.2
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