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Updated: Apr 30, 2026

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
[Protective effects of hyperbaric oxygen treatment on kidney cells of type 2 diabetic rats]
Wen-Jie Nie1, Xiu-Qin Cao, Gui-Qiang Shao
1Wujing Hospital, Shanghai 200241, China. wenjienie@126.com.
Abstract:
The major objective was to explore the effect of early hyperbaric oxygen (HBO) therapy on the tissue structure, apoptosis, and metalloproteinases of kidney cells in Goto-Kakizaki (GK) rats with type 2 diabetes mellitus. GK rats (n = 24) were divided randomly and evenly into model, metformin hydrochloride (MH), and hyperbaric oxygen (HBO) groups, while healthy Wistar rats (n = 8) were used as normal control group. The healthy rats in the normal control group and the GK rats in the model group were both intragastrically administered with purified water (5 mL/kg) once per day. Meanwhile, the rats in the MH group received intragastric administration of MH (250 mg/kg) once daily, while the rats in the HBO group inhaled pure oxygen under a constant pressure (0.15 MPa) for 30 min. After 3 weeks of treatment, the body weight of each rat was measured, and the blood samples were collected from tails. Subsequently, the kidneys of all rats were excised for weighing mass and further examination. For each renal sample, the sections were firstly embedded with paraffin and sliced to prepare histopathologic sections stained using HE, PAS and Masson, respectively, for subsequent observation with optical microscopy. Later, the apoptosis of kidney cells was examined using the TUNEL method by computing the apoptotic index. Furthermore, the histopathologic sections were also examined using the immunohistochemistry approach with Caspase-3, MMP-2, and TIMP-2 antibodies, respectively. At the same time, the plasma concentration of TGF-β1 of the rats in each group was detected using ELISA method. These resultant data showed that the pathological changes of the HBO group were less than those of the model group with respect to increased glomerular volume density of mesangial cells, broadening mesangial matrix and thickening basement membrane as well as swelling renal tubular epithelial cells. The index of cell apoptosis and Caspase-3 expression in the HBO group showed no significant differences (P > 0.05) compared with those in the normal control and MH groups respectively, but demonstrated significant decrease compared with that in the model group (P < 0.01). Meanwhile, the MMP-2 and TIMP-2 expressions of the HBO group were stronger than those in the model and MH groups, but weaker than those in the normal control group (P < 0.05). Although the plasma concentration of TGF-β1 in HBO, MH and model groups was greater than that in the normal control group, no significant statistical difference was distinguished among these four groups (P > 0.05). These results indicate that the HBO treatment can inhibit the apoptosis and Caspase-3 expression of renal cells of GK rats, adjust the activity of MMP-2 and its inhibitors, and reduce the accumulation of extracellular matrix. This implies that the HBO treatment might protect renal tissues, thus delaying occurrence and retaining development of diabetic nephropathy.
Insights
Hyperbaric oxygen (HBO) therapy reduced kidney cell apoptosis and improved tissue structure in diabetic rats. This treatment may protect renal tissues and delay diabetic nephropathy progression.
Area of Science:
- Nephrology
- Diabetology
- Hyperbaric Medicine
Background:
- Type 2 diabetes mellitus (T2DM) is associated with diabetic nephropathy.
- Early intervention is crucial for managing T2DM complications.
- Goto-Kakizaki (GK) rats serve as a model for T2DM.
Purpose of the Study:
- To investigate the effects of early hyperbaric oxygen (HBO) therapy on kidney tissue structure, apoptosis, and metalloproteinases in GK rats with T2DM.
- To compare HBO therapy with metformin hydrochloride (MH) treatment and a control group.
Main Methods:
- GK rats were divided into model, MH, and HBO groups; healthy Wistar rats served as controls.
- Treatments included purified water, MH (250 mg/kg), or HBO (0.15 MPa, 30 min daily) for 3 weeks.
- Kidney tissues were analyzed for histopathology (HE, PAS, Masson staining), apoptosis (TUNEL), Caspase-3, MMP-2, TIMP-2 expression (immunohistochemistry), and plasma TGF-β1 (ELISA).
Main Results:
- HBO therapy reduced pathological changes in kidney tissue compared to the model group.
- HBO significantly decreased kidney cell apoptosis and Caspase-3 expression compared to the model group.
- HBO modulated MMP-2 and TIMP-2 expression, indicating altered extracellular matrix remodeling.
Conclusions:
- Early HBO therapy can inhibit renal cell apoptosis and Caspase-3 expression in GK rats.
- HBO treatment adjusts MMP-2 activity and reduces extracellular matrix accumulation.
- HBO therapy shows potential in protecting renal tissues and delaying diabetic nephropathy development.
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