Abstract: BACKGROUND: Spinal cord injury can cause multi-organ dysfunction, among which intestinal dysfunction seriously affects patients’ disease treatment and quality of life. Some studies have shown that aerobic exercise can improve intestinal structure and function, but the mechanism needs to be further explored. 
OBJECTIVE: To investigate the effect of treadmill training on the function of small intestine in rats with spinal cord injury and its relationship with intestinal cell apoptosis. 
METHODS: The modified spinal cord percussion method was used to prepare a rat model of T10 incomplete spinal cord injury. A total of 54 female Sprague-Dawley rats were randomly divided into a sham-operated group, a model group, and a training group, with 18 rats in each group. The treadmill training was started 7 days after modeling for 3 weeks. After the final intervention, the Basso-Beattie-Bresnahan score and the inclined plate test were used for locomotor testing. Spinal cord tissue samples were taken 0.5 cm above and below the injured site to detect neuronal survival and astrocyte activation levels for testing the effect of exercise on neurological function. The intestinal transport function was evaluated by gavage staining of the first black stool and intestinal staining propulsive efficiency in each group. At 14, 21 and 28 days after spinal cord injury, the pathological structural changes of the small intestine were observed by hematoxylin-eosin staining and the expression of the small intestinal tight junction protein Occludin was detected by immunofluorescence; the expression levels of apoptosis-related proteins Bcl-2, Caspase-9, Bax, Caspase-3, and Cyt-C were detected by western blot.  
RESULTS AND CONCLUSION: Compared with the model group, the training group had recovered neurological function with higher Basso-Beattie-Bresnahan scores and inclined plate angles (P < 0.05), more survived neurons, and less neuroinflammation. At 14 days after spinal cord injury, compared with the sham-operated group, the small intestinal tissue in the model and training groups showed pathological changes, such as mucosal layer disruption, intestinal villus atrophy, reduced number of cup cells, and nuclear consolidation. The pathological damage of the small intestine in the model group peaked at 21 days after spinal cord injury and lasted until the end of the experiment. The pathological changes such as mucosal continuity and intestinal villus atrophy in the training group showed significant improvement at 28 days after surgery. The first black stool time in the training group was lower than that in the model group (P < 0.05), and the intestinal propulsive efficiency was higher than that in the model group (P < 0.05), suggesting that the intestinal transport function improved. At 28 days after spinal cord injury, the expression of the small intestinal tight junction protein Occludin was higher in the training group than the model group (P < 0.01), as well as the Bcl-2 expression (P < 0.05) but the expression of apoptosis-related proteins Caspase-3, Caspase-9, Bax Caspase-9, Bax, and Cyt-C was decreased (P < 0.05). To conclude, the treadmill training can protect the nervous system and small intestinal system in rats with spinal cord injury and the recovery of small intestine function may be related to the level of apoptosis in small intestine tissue.

Key words: spinal cord injury, treadmill, intestinal function, tight junction protein, apoptosis