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Tian-Kui Ma,1,* Li Xu,1,2,* Ling-Xu Lu,1,3,* Xu Cao,1 Xin Li,1 Lu-Lu Li,1 Xu Wang,4 Qiu-Ling Fan1 1Department of Nephrology, The First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Department of Clinical Laboratories, The First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 3The First Respiratory Department, General Hospital of Fushun Mining Bureau, Fushun, Liaoning, People’s Republic of China; 4Department of Gastroenterology, The First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiu-Ling Fan Email cmufql@163.comPurpose: This study aimed to investigate whether ursolic acid (UA) mitigates renal inflammation, oxidative stress and fibrosis by regulating the angiotensin II type 1 receptor-associated protein (ARAP1)/angiotensin II type 1 receptor (AT1R) signaling pathway and subsequently alleviating renal damage.Methods: db/db mice were divided randomly into a diabetic nephropathy (DN) group and a UA treatment group. Light microscopy and electron microscopy were used to observe pathological changes in renal tissues. Immunohistochemistry (IHC) was employed to examine changes in the expression of ARAP1, AT1R, 8-hydroxydeoxyguanosine (8-OHdG), NADPH oxidase 2 (NOX2), the extracellular matrix protein fibronectin (FN), IL-1β and IL-18 in renal tissues. Western blotting and RT-qPCR were used to detect the respective changes in the protein and mRNA levels of ARAP1, AT1R, NOX4, NOX2, transforming growth factor-β1 (TGF-β1), FN, collagen IV, IL-1β and IL-18 in renal tissues and mesangial cells. In addition, immunofluorescence staining was employed to examine changes in FN and NOX2 expression in mesangial cells.Results: UA treatment effectively reduced the body weights and blood glucose levels of db/db mice (p |
