PMID- 35603648 OWN - NLM STAT- MEDLINE DCOM- 20220524 LR - 20220524 IS - 1007-8738 (Print) IS - 1007-8738 (Linking) VI - 38 IP - 5 DP - 2022 May TI - [Saxagliptin alleviates kidney injury in diabetic rats by down-regulating the expression of mammalian target of rapamycin (mTOR)]. PG - 406-411 AB - Objective To investigate the effect of saxagliptin (Sax) against kidney injury in diabetic rats and its mechanisms. Methods SD male rats were fed for 2 weeks, among which 14 rats were selected randomly and given intraperitoneal injection of streptozotocin (STZ) to establish the type 2 diabetes mellitus (T2DM) model, and then were randomly divided into T2DM group and Sax group after the model was successfully established; 6 rats were selected as normal control (NC) group randomly. The rats of Sax group were given the saxagliptin solution. The rats of NC and T2DM groups were injected with the same amount of sodium carboxymethyl cellulose solution. After 8 weeks of continuous gastric administration, the rats were sacrificed and their blood and kidney tissues were collected. Glucose (G1u), albumin (ALB), aspartate transaminase (AST), alanine transaminase (ALT), serum creatinine (Scr), blood urea nitrogen (BUN), uric acid (UA), serum total cholesterol (TC), triglycerides (TG) were detected by automatic biochemical analyzer. HE, PAS, Masson staining and transmission electron microscopy were performed to observe the morphological changes of renal. Immunohistochemical staining was used to detect the protein expression level of mammalian target of rapamycin (mTOR), interleukin 1 (IL-1), IL-6, tumor necrosis factor alpha (TNF-alpha) in renal tissues. Results Compared with the NC group, the levels of biochemical indicators such as G1u, ALB, AST, ALT, Scr, BUN, UA, TC, and TG showed significant increase; the number of glomerular mesangial cells also increased, and the mesangial matrix hyperplasia, mTOR, IL-1, IL-6, TNF-alpha protein expression levels exhibited significant increase in T2DM group. Compared with T2DM group, Sax group showed decreased levels of biochemical indicators such as G1u, ALB, AST, ALT, Scr, BUN, UA, TC, and TG and improved renal pathological damage performance, together with a profound reduction in mTOR, IL-1, IL-6, TNF-alpha protein expression level. Conclusion Sax may suppress inflammatory response and reduce renal injury in diabetic rats by down-regulating mTOR expression. FAU - Ni, Wenjing AU - Ni W AD - Department of Nephrology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China. FAU - Pan, Yan AU - Pan Y AD - Department of Nephrology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China. FAU - Yang, Huijuan AU - Yang H AD - Department of Nephrology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China. FAU - Li, Wei AU - Li W AD - Department of Nephrology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China. FAU - Sun, Yan AU - Sun Y AD - School of Clinical Medicine, Bengbu Medical College, Bengbu 233000, China. FAU - Xu, Yu AU - Xu Y AD - School of Life Science, Bengbu Medical College, Bengbu 233000, China. FAU - Chen, Weidong AU - Chen W AD - Department of Nephrology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China. *Corresponding author, E-mail: cwd2012@163.com. LA - chi 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 (Dipeptides) RN - 0 (Interleukin-1) RN - 0 (Interleukin-6) RN - 0 (Tumor Necrosis Factor-alpha) RN - 9GB927LAJW (saxagliptin) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - PJY633525U (Adamantane) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Adamantane/analogs & derivatives MH - Animals MH - *Diabetes Mellitus, Experimental/complications/drug therapy MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Dipeptides MH - Interleukin-1/metabolism MH - Interleukin-6/metabolism MH - Kidney/pathology MH - Male MH - Mammals MH - Rats MH - Sirolimus/pharmacology MH - TOR Serine-Threonine Kinases/metabolism MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2022/05/24 06:00 MHDA- 2022/05/25 06:00 CRDT- 2022/05/23 06:17 PHST- 2022/05/23 06:17 [entrez] PHST- 2022/05/24 06:00 [pubmed] PHST- 2022/05/25 06:00 [medline] PST - ppublish SO - Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2022 May;38(5):406-411.