PMID- 38284253 OWN - NLM STAT- MEDLINE DCOM- 20240130 LR - 20240131 IS - 1007-8738 (Print) IS - 1007-8738 (Linking) VI - 40 IP - 2 DP - 2024 Feb TI - [Empagliflozin inhibits inflammatory response and alleviates renal injury in type 2 diabetic rats by up-regulating the expression of exchange protein 1 directly activated by cAMP (Epac1)]. PG - 129-134 AB - Objective To observe the therapeutic effect of empagliflozin (EM) on renal injury in rats with type 2 diabetes mellitus (T2DM), and to explore its possible mechanism. Methods Male SD rats were randomly divided into a normal control (NC) group, a T2DM group, and an EM group, with 6 rats in each group. T2DM models were established by an intraperitoneal injection of streptozotocin (STZ) in the T2DM and EM groups. Fasting blood glucose (FBG) levels and body mass of rats in each group were recorded. The EM group received EM solution through intragastric administration, while the other two groups were given an equivalent volume of sodium carboxymethyl cellulose solution through intragastric administration for 12 weeks. After the body mass and FBG levels were recorded, the rats were sacrificed and blood samples from the abdominal aorta and kidney tissues were collected. Serum creatinine (Scr), blood urea nitrogen (BUN), uric acid (UA), triglyceride (TG) and total cholesterol (TC) were detected by automatic biochemical analyzer. Masson, PAS and HE staining were used to assess histological changes in the kidneys, and a transmission electron microscopy was used to observe ultrastructural changes. Immunohistochemical staining was used to detect the expression and distribution of exchange protein 1 directly activated by cAMP(Epac1), TNF-alpha, IL-1beta, and IL-18 in renal tissue of rats. Results Compared with the NC group, the rats in T2DM group showed a decrease in body mass, a significant increase in the levels of FBG, Scr, BUN, UA, TC, and TG, thickened glomerular basement membrane, foot process fusion of podocytes, disordered cell arrangement and loss of endothelial cell fenestrations. The expression level of Epac1 decreased, while the expression levels of TNF-alpha, IL-1beta, and IL-18 significantly increased. Compared with the T2DM group, the rats in the EM group showed an increase in body mass, significantly decreased levels of FBG, Scr, BUN, UA, TC, and TG, reduced renal injury, increased expression level of Epac1, and significantly decreased expression levels of TNF-alpha, IL-1beta, and IL-18. Conclusion EM can improve renal injury in T2DM rats by up-regulating Epac1 expression to inhibit inflammatory response. FAU - Qian, Yuchi AU - Qian Y AD - Department of Nephrology, First Affiliated Hospital of Bengbu Medical University, Bengbu Medical University, Bengbu 233000, China. FAU - Wan, Lu AU - Wan L AD - Department of Nephrology, First Affiliated Hospital of Bengbu Medical University, Bengbu Medical University, Bengbu 233000, China. FAU - Lu, Yuxin AU - Lu Y AD - Department of Nephrology, First Affiliated Hospital of Bengbu Medical University, Bengbu Medical University, Bengbu 233000, China. FAU - Ni, Wenjing AU - Ni W AD - Department of Nephrology, First Affiliated Hospital of Bengbu Medical University, Bengbu Medical University, Bengbu 233000, China. FAU - Yang, Huijuan AU - Yang H AD - Experimental Center of Clinical Laboratory Diagnostics, Bengbu Medical University, Bengbu 233000, China. FAU - Pan, Yan AU - Pan Y AD - Functional Science laboratory, School of Basic Medicine, Bengbu Medical University, Bengbu 233000, China. FAU - Chen, Weidong AU - Chen W AD - Department of Nephrology, First Affiliated Hospital of Bengbu Medical University, Bengbu Medical University, Bengbu 233000, China. *Corresponding author, E-mail: cwd2012@163.com. LA - chi PT - English Abstract PT - Journal Article PL - China TA - Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi JT - Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology JID - 101139110 RN - 0 (Interleukin-18) RN - HDC1R2M35U (empagliflozin) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) SB - IM MH - Rats MH - Male MH - Animals MH - Rats, Sprague-Dawley MH - Interleukin-18/metabolism MH - *Diabetes Mellitus, Type 2/complications MH - *Diabetes Mellitus, Experimental/drug therapy MH - Tumor Necrosis Factor-alpha/metabolism MH - Kidney MH - *Diabetic Nephropathies/drug therapy/etiology MH - *Benzhydryl Compounds MH - *Glucosides EDAT- 2024/01/29 06:43 MHDA- 2024/01/30 12:42 CRDT- 2024/01/29 05:29 PHST- 2024/01/30 12:42 [medline] PHST- 2024/01/29 06:43 [pubmed] PHST- 2024/01/29 05:29 [entrez] PST - ppublish SO - Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2024 Feb;40(2):129-134.