High-Intensity Interval Training Attenuates Inflammation in Cardiorenal Syndrome Induced by Renal Ischemia–Reperfusion Injury in Rats

Figures

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  Figure 1. Experimental design. Thirty male Sprague–Dawley rats were randomly assigned to the Sham, renal ischemia–reperfusion (I/R), and high-intensity interval training (HIIT) groups at 3 weeks of age. Rats in the HIIT group underwent 2 weeks of adaptation training followed by 4 weeks of HIIT before renal I/R surgery. All rats were sacrificed 24 h after the surgical procedure.

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  Figure 2. Effects of HIIT on renal function. Renal ischemia–reperfusion (I/R) significantly increased (A) blood urea nitrogen (BUN) and (B) creatinine levels compared with the sham group, whereas HIIT reduced these elevations. Data are presented as mean ± SD (n = 6 per group). ★★ p < 0.01 vs. SHAM; && p < 0.01 vs. Renal I/R. I/R, ischemia–reperfusion; HIIT, high-intensity interval training.

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  Figure 3. (A) Representative H&E-stained kidney sections (400× magnification). SHAM kidneys show normal glomeruli and tubules. Renal I/R kidneys show glomerular dilation and structural disruption (black arrows), and tubular necrosis/dilation (red arrows). HIIT kidneys showed partial improvement in tubular morphology (red arrows), whereas glomerular abnormalities persisted. (B,C) Quantitative tubular and glomerular injury scores. Data are presented as mean ± SD (n = 4). ★ p < 0.05 vs. SHAM; & p < 0.05 vs. renal I/R (tubular score only). I/R, ischemia–reperfusion; HIIT, high-intensity interval training.

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  Figure 4. Serum markers of myocardial injury. Levels of (A) creatine phosphokinase (CPK), (B) cardiac troponin I (cTnI), and (C) lactate dehydrogenase (LDH) were significantly elevated in the renal ischemia–reperfusion (I/R) group compared with the sham group. HIIT reduced these elevations. Data are presented as mean ± SD (n = 6 per group). ★★ p < 0.01 vs. SHAM; && p < 0.01 vs. renal I/R. I/R, ischemia–reperfusion; HIIT, high-intensity interval training.

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  Figure 5. (A) Representative H&E-stained myocardial sections (400×) from the SHAM, renal ischemia–reperfusion (I/R), and HIIT groups. SHAM myocardium shows normal, well-aligned fibers without edema or disruption. Renal I/R myocardium exhibits marked interstitial edema and waviness/disruption of cardiomyocyte fibers (black arrow). HIIT myocardium shows mild interstitial edema and fiber disarray, qualitatively less pronounced than in the renal I/R group (black arrow). (B) Quantification of myocardial injury scores. Data are presented as mean ± SD (n = 4 per group). ★ p < 0.05 vs. SHAM. I/R, ischemia–reperfusion; HIIT, high-intensity interval training.

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  Figure 6. (A) Representative TUNEL-stained myocardial sections (400× magnification). SHAM myocardium shows almost no TUNEL-positive nuclei. Renal I/R myocardium exhibits numerous TUNEL-positive apoptotic nuclei (red arrows). HIIT myocardium shows multiple TUNEL-positive nuclei, although qualitatively fewer than those observed in the renal I/R group (red arrows). (B) Quantification of TUNEL-positive cells. Data are presented as mean ± SD (n = 4). ★ p < 0.05 vs. SHAM. I/R = ischemia–reperfusion; HIIT = high-intensity interval training.

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  Figure 7. Serum cytokine levels measured by ELISA. Renal ischemia–reperfusion (I/R) markedly increased serum (A) TNF-α, (B) IL-1β, and (C) IL-6 levels compared with the sham group, while (D) IL-10 levels were significantly reduced. HIIT significantly attenuated the elevations of TNF-α, IL-1β, and IL-6, and partially restored IL-10 levels compared with the renal I/R group. Data are presented as mean ± SD (n = 6 per group). ★★ p < 0.01 vs. SHAM; && p < 0.01 vs. renal I/R. I/R, ischemia–reperfusion; HIIT, high-intensity interval training.

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  Figure 8. Western blot analysis of myocardial proteins. Representative blots and quantification of (A) activated caspase-3, (B) TNF-α, and (C) Bax expression in the myocardium. Protein levels were normalized to that of β-actin. Renal ischemia–reperfusion (I/R) significantly increased caspase-3, TNF-α, and Bax levels compared with the sham group. HIIT reduced caspase-3 and TNF-α expression and showed a slight, non-significant reduction in Bax. Data are presented as mean ± SD (n = 4 per group). ★ p < 0.05 vs. SHAM. & p < 0.05 vs. renal I/R. I/R, ischemia–reperfusion; HIIT, high-intensity interval training.