Abstract: BACKGROUND: Renal fibrosis is the main characteristic and basic pathophysiological change of chronic renal failure, in which local imbalance of renin-angiotensin system homeostasis induced abnormal collagen metabolism may play a key role. Aerobic exercise is an important non-drug method for the prevention and treatment of various types of tissue fibrosis; however, its effect and mechanism on renal fibrosis have not been clarified. 
OBJECTIVE: To elucidate the effect of regular aerobic exercise on renal fibrosis in a rat model of chronic renal failure and to explore the mechanism of collagen metabolic pathway and renin-angiotensin system. 
METHODS: Forty-five 6-week-old male Sprague-Dawley rats were randomly divided into sham group, model sedentary group, and model exercise group, with 15 rats in each group. Animal models of chronic renal failure were established by 5/6 nephrectomy in the latter two groups. The sham and model sedentary groups were caged and fed quietly, while the model exercise group received 18 weeks of treadmill aerobic exercise training (60 minutes a day, 5 days per week). After exercise, caudal artery blood pressure was measured by non-invasive sphygmomanometer; urine was collected from metabolic cage for 24-hour proteinuria measurement; and blood sample was taken from the heart to detect serum urea nitrogen and serum creatinine. Renal histopathology was observed by periodic acid–Schiff and Masson staining, and glomerular sclerosis index and fibrosis index were obtained. Protein expression of type I collagen, transforming growth factor-β1, matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, angiotensinogen, renin, renin receptor, angiotensin converting enzyme, angiotensin converting enzyme 2, angiotensin II type 1 receptor, angiotensin II type 2 receptor, and Mas receptor in kidney tissue was determined by western blot. The activity of matrix metalloproteinase-2 and matrix metalloproteinase-9 in kidney tissue was detected by gelatin zymography. 
RESULTS AND CONCLUSION: Compared with the model sedentary group, in model exercise group, blood pressure was decreased and renal function was improved (P < 0.05), glomerulosclerosis index and renal fibrosis index values were reduced (P < 0.05), the protein expressions of type I collagen, transforming growth factor-β1, tissue inhibitor of metalloproteinase-1, angiotensinogen, renin, angiotensin converting enzyme and angiotensin II type 1 receptor were downregulated (P < 0.05), the protein expression of matrix metalloproteinase-2, matrix metalloproteinase-9, angiotensin converting enzyme 2, angiotensin II type 2 receptor, and Mas receptor was upregulated (P < 0.05), the ratio of matrix metalloproteinase-2/tissue inhibitor of metalloproteinase-1, the ratio of matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 and the activity of matrix metalloproteinase-2 in kidney tissue were increased (P < 0.05). To conclude, long-term aerobic exercise can alleviate renal fibrosis and delay the progression of renal failure induced by 5/6 nephrectomy in rats, and the mechanism may be related to the restoration of renin-angiotensin system homeostasis imbalance and improvement of collagen metabolism.

Key words: aerobic exercise, chronic renal failure, renal fibrosis, extracellular matrix, renin-angiotensin system