Exploring the Effect of Dapagliflozin on Alcoholic Kidney Injury and Renal Interstitial Fibrosis in Rats Based on TIMP-1/MMP-24 Pathway

Objective. To establish a rat model of alcoholic kidney injury and detect the expression of TIMP-1/MMP-24 in the kidneys of rats with alcoholic kidney injury at the molecular pathological level, so as to explore the mechanism of alcohol abuse leading to kidney injury and renal interstitial fibrosis...

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Bibliographic Details
Published in:Evidence-based complementary and alternative medicine 2021, Vol.2021, p.6538189-8
Main Authors: Wu, Yundou, Song, Peijun, Yuan, Xinke, Li, Dayong
Format: Article
Language:English
Subjects:
Abuse
Alcohol
Alcohol abuse
Antidiabetics
Blood
Blood vessels
Creatinine
Cytokines
Drug abuse
Enzymes
Evidence-based medicine
Fibroblasts
Fibrosis
Glucose
Growth factors
Inflammation
Interleukin 6
Kidneys
Proteins
Signal transduction
Smad3 protein
Tissue inhibitor of metalloproteinase 1
Transforming growth factor-b1
Tumor necrosis factor-TNF
Tumor necrosis factor-α
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Summary:Objective. To establish a rat model of alcoholic kidney injury and detect the expression of TIMP-1/MMP-24 in the kidneys of rats with alcoholic kidney injury at the molecular pathological level, so as to explore the mechanism of alcohol abuse leading to kidney injury and renal interstitial fibrosis as well as the alleviation of alcohol-induced kidney injury and inhibition of renal interstitial fibrosis by dapagliflozin. Methods. 48 male rats were randomly divided into 4 groups: control group, alcohol group, alcohol + dapagliflozin group, and alcohol + losartan group, each with 12 rats. Different drugs were administered by gavage for modeling and treatment. Six days later, the rats were sacrificed, blood was collected from the heart to separate the serum, and the blood creatinine (Scr) and urea nitrogen (BUN) contents were detected biochemically. After blood collection, the kidney tissue was taken and fixed in10% neutral formalin. The expression of renal tissue inflammatory factors (CRP, IL-6, and TNF-α) and renal fibrosis indexes (LN, HA, and TGF-β1) were detected; MMP-24 and TIMP-1 in the kidney tissue of rats in different treatment groups were detected, and Smad3 expression was also detected. Results. After treatment, the general condition of the alcohol + dapagliflozin group and the alcohol + losartan group improved to different degrees. The weight first decreased and then gradually increased over time. There was no statistical difference in the weight change between the two groups; Compared with the control group, the Scr level, BUN content, renal index, inflammatory factors, and renal fibrosis indexes in the alcohol group were significantly increased (P
ISSN:1741-427X
1741-4288
DOI:10.1155/2021/6538189