中国临床药理学杂志2025,Vol.41Issue(6):828-833,6.DOI:10.13699/j.cnki.1001-6821.2025.06.015
苯扎贝特对糖尿病肾病小鼠肾组织的保护作用
Research on the protective effects of bezafibrate on the kidney tissue of mice with diabetic nephropathy
摘要
Abstract
Objective To investigate the mechanism of action of bezafibrate(BEZ)targeting nuclear factor of activated T cells 5(NFAT5)through microribonucleic acid(miR)-486-5p on the kidney tissues of mice with diabetic nephropathy.Methods Db/m mice were used as control group.Db/db mice were used to construct a diabetic nephropathy model,which was divided into 4 groups according to the random number table method:Model group,experimental group(75 mg·kg-1·d-1 BEZ),miR-486-5p antagomir group(75 mg·kg-1·d-1 BEZ+10 mg·kg-1 miR-486-5p antagomir),sh-NFAT5 group(75 mg·kg-1·d-1 BEZ+10 mg·kg-1 miR-486-5p antagomir+recombinant adenovirus containing NFAT5 knockdown plasmid).The kit was used to detect the levels of renal function and oxidative stress in mice;and the expression levels of glucose metabolism and renal fibrosis-related proteins in renal tissues of mice in each group were detected by Western blot.Results The levels of malondialdehyde(MDA)in the control group,model group,experimental group,miR-486-5p antagomir group,and sh-NFAT5 group were(2.78±0.56),(4.96±0.97),(3.02±0.54),(4.51±0.79)and(3.24±0.58)nmol·mg-1,respectively;the levels of aldose reductase(AR)were 1.00±0.12,3.61±0.43,1.82±0.29,3.09±0.58 and 2.25±0.47,respectively;the levels of pyruvate dehydrogenase(PDH)were 1.00±0.11,0.53±0.10,0.91±0.15,0.64±0.12 and 0.82±0.14,respectively;the levels of pyruvate dehydrogenase E1 subunit α1(PDHA1)were 1.00±0.14,0.36±0.07,0.83±0.16,0.51±0.11 and 0.74±0.13,respectively;the levels of pyruvate dehydrogenase kinase(PDK)were 1.00±0.10,2.59±0.52,1.34±0.31,2.11±0.43 and 1.56±0.39,respectively;the levels of transforming growth factor-β1(TGF-β1)were 1.00±0.11,3.15±0.52,1.43±0.38,2.72±0.43 and 1.89±0.57,respectively;the levels of fibronectin(FN)were 1.00±0.09,2.84±0.57,1.46±0.41,2.59±0.52 and 1.73±0.49,respectively;the levels of collagen type Ⅰ(Collagen Ⅰ)were 1.00±0.13,4.28±0.71,2.03±0.46,3.64±0.68 and 2.51±0.53,respectively.The above indicators of the control group were compared with the model group,the above indicators of the model group were compared with the experimental group,the above indicators of the experimental group were compared with the miR-486-5p antagomir group,and the above indicators of the miR-486-5p antagomir group were compared with the sh-NFAT5 group.The differences were statistically significant(P<0.05,P<0.01,P<0.001).Conclusion BEZ can effectively protect the kidney tissue of mice with diabetic nephropathy,and the mechanism may be realized through the miR-486-5p/NFAT5 signaling pathway.关键词
苯扎贝特/微小核糖核酸-486-5p/糖尿病肾病/活化T细胞的核因子5/氧化应激/肾纤维化Key words
bezafibrate/microRNA-486-5p/diabetic nephropathy/nuclear factor of activated T cells 5/oxidative stress/renal fibrosis分类
医药卫生引用本文复制引用
罗根艳,董林菲,杨栋梁,刘媛,杨子琦,钟燕,龚志坚..苯扎贝特对糖尿病肾病小鼠肾组织的保护作用[J].中国临床药理学杂志,2025,41(6):828-833,6.基金项目
江西省卫生健康委科技计划基金资助项目(202311860) (202311860)