Functional mechanism of AMPK activation in mitochondrial regeneration of rat peritoneal macrophages mediated by uremic serum

OBJECTIVE: To investigate the effects of AMPK activation on mitochondrial inhibition by uremic serum through the AMPK-activated rat peritoneal macrophages stimulated by uremic serum, thereby providing a reference for the clinical treatment of chronic kidney disease. METHODS: Twenty-two male Sprague-Dawley (SD) rats were included as experimental subjects. Fifteen rats were constructed into chronic kidney disease models (the model group). The remaining seven rats only received renal capsule stripping instead of nephrectomy (the sham-operated group). Ten weeks after model construction, the bodyweight, blood biochemical indicators, and metabolic parameters of rats in groups were measured. Meanwhile, the expression of the M1 phenotype marker protein in peritoneal macrophages was determined. RESULTS: Ten weeks after model construction, the bodyweight of rats in the model group was significantly lower than that in the sham-operated group. The values of urea nitrogen and serum creatinine were significantly higher than those in the sham-operated group (P<0.01). The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and the monocyte chemoattractant protein 1 (MCP-1) of rats in the model group were significantly higher than those in the sham-operated group (P <0.01). After the lipopolysaccharide (LPS) stimulation, the expressions of M1 phenotype marker mRNA in the model group was significantly increased. The expression of mitochondrial structural protein mRNA in the peritoneal macrophages of rats in the model group was significantly lower than that in the sham-operated group. The expression of M1 phenotype marker mRNA was significantly decreased in the uremic serum group after AMPK agonist (P<0.01). CONCLUSION: In rats with chronic renal insufficiency, mitochondrial regeneration was dysfunctional in macrophages. By activating AMPK, the inhibitory effect of uremia serum on mitochondrial regeneration of macrophages was improved. Therefore, AMPK was a critical factor that could regulate mitochondrial regeneration of macrophages.