PMID- 31631599 OWN - NLM STAT- MEDLINE DCOM- 20191114 LR - 20220411 IS - 1672-173X (Print) IS - 1672-173X (Linking) VI - 50 IP - 3 DP - 2019 May TI - [Renal Injury and Its Mechanisms in Lepr (db/ db) Mice]. PG - 334-338 AB - OBJECTIVE: To study the mechanism of renal injury in Lepr (db/ db) mice with the leptin receptor homozygous deficiency. METHODS: Ten male of 28-week-old Lepr (db/+) mice with leptin receptor heterozygous deficiency were selected as control group and ten male Lepr (db/ db) mice with leptin receptor homozygous deficiency were used in this study. After fasting for 8 hours, the body mass, fasting blood glucose (FBG) and glycosylated hemoglobulin (HbA1c) of the mice were measured. Blood of the mice was obtained from femoral artery before euthanasia. Serum creatinine (CRE), blood urea nitrogen (BUN), superoxide dismutase (SOD), glutathione (GSH) and malonaldehyde (MDA) were detected by corresponding kits, and serum interleukin-1beta (IL-1beta), monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) were measured using enzyme-linked immunosorbent assay (ELISA) method. The kidney was taken for pathological observation. The expression levels of nuclear factor E2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-kappaB) in renal were analyzed by Western blot. The mitochondria of renal was isolated by the corresponding kit. Meanwhile, the expression level of lipoic acid synthase (LIAS) in renal mitochondria was measured by Western blot. RESULTS: The body mass, FPG, HbA1c, CRE and BUN levels of the Lepr (db/ db) mice were significantly increased in comparison with the Lepr (db/+) mice ( P<0.05). Compared with the Lepr (db/+) mice, the Lepr (db/ db) mice renal exhibited glomerular hypertrophy, thickened basement membrane and capillary wall, the mesangial matrix expansion and mesangial cell hyperplasia. Compared with the Lepr (db/+) mice, the serum level of GSH in the Lepr (db/ db) mice was decreased significantly ( P<0.05). The levels of MDA and concentrations of MCP-1, IL-1beta and TNF-alpha in serum of the Lepr (db/ db) mice were higher than those of the Lepr (db/+) mice ( P<0.05). Compared with the Lepr (db/+) mice, the expression of LIAS and Nrf2 protein in the Lepr (db/ db) mice renal were decreased ( P<0.05), while the expression of NF-kappaB protein was increased ( P<0.05). CONCLUSION: LIAS, Nrf2 and NF-kappaB might play significant roles through regulation of oxidative stress and inflammation in the renal injury of Lepr (db/ db) mice. CI - Copyright(c) by Editorial Board of Journal of Sichuan University (Medical Science Edition). FAU - Yan, Ting-Ting AU - Yan TT AD - Department of Toxicology, School of Public Health, Xinxiang Medical University, Xinxiang 453003, China. FAU - Xu, Guang-Cui AU - Xu GC AD - Department of Toxicology, School of Public Health, Xinxiang Medical University, Xinxiang 453003, China. FAU - Peng, Qiang AU - Peng Q AD - Department of Toxicology, School of Public Health, Xinxiang Medical University, Xinxiang 453003, China. FAU - Wu, Wei-Dong AU - Wu WD AD - Department of Toxicology, School of Public Health, Xinxiang Medical University, Xinxiang 453003, China. FAU - Yi, Xian-Wen AU - Yi XW AD - Department of Toxicology, School of Public Health, Xinxiang Medical University, Xinxiang 453003, China. FAU - Zhao, Ying-Zheng AU - Zhao YZ AD - Department of Toxicology, School of Public Health, Xinxiang Medical University, Xinxiang 453003, China. LA - chi PT - Journal Article PL - China TA - Sichuan Da Xue Xue Bao Yi Xue Ban JT - Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition JID - 101162609 RN - 0 (NF-E2-Related Factor 2) RN - 0 (NF-kappa B) RN - 0 (Nfe2l2 protein, mouse) RN - 0 (Receptors, Leptin) RN - EC 2.8.1.- (Sulfurtransferases) RN - EC 2.8.1.- (lipoic acid synthase) SB - IM MH - Animals MH - Kidney/*pathology MH - Male MH - Mice MH - Mice, Knockout MH - NF-E2-Related Factor 2/*metabolism MH - NF-kappa B/*metabolism MH - Oxidative Stress MH - Receptors, Leptin/*genetics MH - Sulfurtransferases/*metabolism OTO - NOTNLM OT - LIAS OT - Leprdb/db mice OT - NF-kappaB OT - Nrf2 OT - Renal injury EDAT- 2019/10/22 06:00 MHDA- 2019/11/15 06:00 CRDT- 2019/10/22 06:00 PHST- 2019/10/22 06:00 [entrez] PHST- 2019/10/22 06:00 [pubmed] PHST- 2019/11/15 06:00 [medline] PST - ppublish SO - Sichuan Da Xue Xue Bao Yi Xue Ban. 2019 May;50(3):334-338.