非奈利酮通过抗炎抗氧化改善糖尿病肾病大鼠血脂代谢OA

Objective To investigate the effect of finerenone on lipid metabolism in experimental DKD in rats.Methods A total of 24 male SPF-grade SD rats were acclimatized for 2 weeks.Six rats were randomly selected as the normal control group and given a normal diet.The remaining rats were induced with diabetic kidney disease by administration of streptozotocin combined with a high-fat,high-sugar diet.After successful model establishment,rats were randomly divided into the model group,low-dose finerenone group,and high-dose finerenone group.All rats were given a high-fat,high-sugar diet and drug interventions,with the low-dose and high-dose finerenone groups receiving 5 mg/kg and 10 mg/kg of finerenone,respectively.After the intervention period,blood samples were collected from the abdominal aorta to measure blood lipid profile indicators(total cholesterol[TC],triglyceride[TG],high-density lipoprotein cholesterol[HDL-C],low-density lipoprotein cholesterol[LDL-C],free fatty acid[FFA]),oxidative stress markers(catalase[CAT],malondialdehyde[MDA],superoxide dismutase[SOD]),and inflammatory factors(interleukin-6[IL-6],tumor necrosis factor-α[TNF-α],adiponectin[ADPN],C-reactive protein[CRP]).Liver and kidney tissues were harvested for HE and Oil Red O staining to observe pathological changes.Results Compared to the normal control group,the body weight of the model group was decreased(P<0.001),and the liver weight,liver index,and glycated hemoglobin l evels were significantly increased(P<0.001).Blood lipid profile indicators,including TC,LDL-C,FFA,and TG,were significantly elevated(P<0.05),while HDL-C was significantly reduced(P<0.001).Oxidative stress markers,including CAT and SOD,were significantly lower(P<0.001),and MDA levels were significantly higher(P<0.001).Inflammatory factors,including IL-6,TNF-α,ADPN,and CRP,were all significantly elevated(P<0.001).Compared to the model group,finerenone-treated groups showed significant reductions in TC,LDL-C,FFA,MDA,IL-6,TNF-α,ADPN,CRP,ALT,and AST levels(P<0.05),while HDL-C,CAT,and SOD levels were significantly elevated(P<0.05).Liver lipid deposition was improved,and pathological changes in the kidneys were ameliorated.Conclusion Finerenone can improve lipid metabolism in diabetic kidney disease rats by downregulating TC,LDL-C and upregulating HDL-C.The mechanism may involve the inhibition of oxidative stress and inflammation,as well as the improvement of renal tubular lipid metabolism.