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Updated: Jan 5, 2026
Ischemia-reperfusion Model of Acute Kidney Injury and Post Injury Fibrosis in Mice
Published on: August 9, 2013
[Renal Injury and Its Mechanisms in Lepr Mice]
Ting-Ting Yan1, Guang-Cui Xu1, Qiang Peng1
1Department of Toxicology, School of Public Health, Xinxiang Medical University, Xinxiang 453003, China.
Objective:
To study the mechanism of renal injury in Lepr mice with the leptin receptor homozygous deficiency.
Methods:
Ten male of 28-week-old Lepr mice with leptin receptor heterozygous deficiency were selected as control group and ten male Lepr 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-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) 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-κB) 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 mice were significantly increased in comparison with the Lepr mice ( P<0.05). Compared with the Lepr mice, the Lepr mice renal exhibited glomerular hypertrophy, thickened basement membrane and capillary wall, the mesangial matrix expansion and mesangial cell hyperplasia. Compared with the Lepr mice, the serum level of GSH in the Lepr mice was decreased significantly ( P<0.05). The levels of MDA and concentrations of MCP-1, IL-1β and TNF-α in serum of the Lepr mice were higher than those of the Lepr mice ( P<0.05). Compared with the Lepr mice, the expression of LIAS and Nrf2 protein in the Lepr mice renal were decreased ( P<0.05), while the expression of NF-κB protein was increased ( P<0.05).
Conclusion:
LIAS, Nrf2 and NF-κB might play significant roles through regulation of oxidative stress and inflammation in the renal injury of Lepr mice.
Insights
Leptin receptor homozygous deficiency in mice leads to increased body mass, blood glucose, and kidney injury markers. Lipoic acid synthase, Nrf2, and NF-κB are implicated in this renal damage.
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- Leptin receptor (Lepr) deficiency is associated with metabolic dysfunction.
- Understanding the mechanisms of renal injury in Lepr deficiency is crucial for metabolic disease research.
Purpose of the Study:
- To investigate the pathological mechanisms of renal injury in mice with homozygous leptin receptor deficiency (Lepr-/-).
Main Methods:
- Compared biochemical and pathological parameters between Lepr-/- mice and heterozygous controls.
- Assessed serum markers of kidney function, oxidative stress, and inflammation.
- Analyzed renal expression of key proteins involved in oxidative stress and inflammation pathways (Nrf2, NF-κB, LIAS).
Main Results:
- Lepr-/- mice exhibited significantly elevated body mass, fasting blood glucose, HbA1c, creatinine, and BUN.
- Renal pathology in Lepr-/- mice included glomerular hypertrophy, thickened membranes, mesangial expansion, and cell hyperplasia.
- Decreased GSH and increased MDA, MCP-1, IL-1β, and TNF-α were observed in Lepr-/- mice serum.
- Renal expression of LIAS and Nrf2 was decreased, while NF-κB expression was increased in Lepr-/- mice.
Conclusions:
- Leptin receptor deficiency induces significant renal injury characterized by metabolic dysregulation, oxidative stress, and inflammation.
- Lipoic acid synthase (LIAS), Nrf2, and NF-κB signaling pathways are critically involved in the pathogenesis of renal injury in Lepr-/- mice.
