Protective Effects of Bariatric Surgery on Kidney Functions by Inhibiting Oxidative Stress Responses Through
Hong-Wei Jiang1, Yong Zhou1, Pin-Yi Zhou1
1Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
Objective:
The aim of this study was to explore the protective effects and the regulatory mechanisms of bariatric surgery on kidney injury in diabetic rats.
Methods:
We established a useful type 2 diabetic rat model using high-fat and high-sugar diet feeding following low-dose streptozotocin (STZ) treatment. Sprague-Dawley (SD) rats were randomly divided into the following groups: control (Con) group, diabetic nephropathy (DN) group, and duodenal-jejunal bypass (DJB) surgery group. The food intake and body weight of rats were monitored and the glucose tolerance test (OGTT) test was performed every 2 weeks. The glomerular filtration rate (GFR) and urinary albumin excretion rate (UAFR) were measured to assess renal function. Hematoxylin-eosin (H&E), periodic acid-Schiff (PAS), and Masson staining were used to evaluate renal histopathological changes. TUNEL assay was performed to detect cell apoptosis. The expressions of oxidative stress factors and inflammatory factors in the renal tissues of rats were detected by ELISA. The expressions of PPARα, reactive oxygen species (ROS), and NF-κB were detected by immunofluorescence. For in vitro experiment, HK2 cells cultured with high glucose were treated with PPARα agonist, PPARα antagonist, and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) agonist. The expressions of AMPK/PPARα/NF-κB signaling pathway-related proteins were detected by Western blot.
Results:
Bariatric surgery improved the glucose tolerance of DN rats. The GFR was decreased, the promotion of urinary albumin excretion rate (UAER) was inhibited, and the renal injury was alleviated. The extracellular matrix fraction was decreased and the renal function was improved. Meanwhile, bariatric surgery activates PPARα, inhibits ROS release, reduces oxidative stress injury, and reduces renal cell apoptosis. In vitro experiment results showed that the AMPK activator could activate PPARα, downregulate NF-κB, and inhibit inflammatory response. The phosphorylation of AMPK was inhibited by PPARα antagonism.
Conclusion:
Bariatric surgery can activate PPARα, inhibit oxidative stress injury, and improve glucose metabolism and renal function in DN rats.
Insights
Bariatric surgery protects against kidney injury in diabetic rats by improving glucose metabolism and activating PPARα. This intervention reduces oxidative stress and inflammation, offering a potential therapeutic strategy for diabetic nephropathy.
Area of Science:
- Nephrology
- Metabolic Surgery
- Diabetology
Background:
- Diabetic nephropathy (DN) is a major complication of type 2 diabetes.
- Understanding protective mechanisms against DN is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the protective effects of bariatric surgery on kidney injury in diabetic rats.
- To elucidate the regulatory mechanisms underlying these protective effects.
Main Methods:
- A type 2 diabetic rat model was established using streptozotocin (STZ) and a high-fat/high-sugar diet.
- Rats underwent duodenal-jejunal bypass (DJB) surgery, and renal function was assessed via glomerular filtration rate (GFR) and urinary albumin excretion rate (UAER).
- Histopathological changes, apoptosis, oxidative stress, and inflammatory markers (PPARα, ROS, NF-κB) were analyzed using various assays and staining techniques, including in vitro studies with HK2 cells.
Main Results:
- Bariatric surgery significantly improved glucose tolerance and alleviated renal injury in diabetic rats.
- DJB surgery led to improved GFR, reduced UAER, decreased extracellular matrix, and inhibited renal cell apoptosis.
- The surgery activated PPARα, inhibited reactive oxygen species (ROS) release, and reduced oxidative stress and inflammation, with in vitro results supporting the AMPK/PPARα pathway's role.
Conclusions:
- Bariatric surgery demonstrates protective effects against kidney injury in diabetic rats.
- The mechanism involves activation of PPARα, inhibition of oxidative stress, and improvement of glucose metabolism and renal function.
- These findings highlight bariatric surgery as a potential therapeutic approach for managing diabetic nephropathy.
Related Concept Videos
01:20Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion
01:26Kidney Transplant II: Surgical Procedure