Protective effect of tauroursodeoxycholic acid on the autophagy of nerve cells in rats with acute spinal cord injury

L. Miao, Y. Dong, F.-B. Zhou, Y.-L. Chang, Z.-G. Suo, H.-Q. Ding

Department of Orthopedics, Ningxia People’s Hospital Yinchuan, Ningxia, China. dinghuiqiangnx@sina.com

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• Pharmacology

OBJECTIVE: To investigate the impact and protective effect of tauroursodeoxycholic acid (TUDCA) on the autophagy of nerve cells in rats with acute spinal cord injury.

MATERIALS AND METHODS: Seventy-two 6-8-week-old male Sprague-Dawley (SD) rats were selected and were randomly divided into a sham operation group, a saline control group and a TUDCA treatment group (high and low dose groups). The experimental animals were sacrificed at 24 hours, 5 days and 10 days after spinal cord injury. The Basso, Beattie, Bresnahan locomotor scale was used to assess the hind limb locomotor function after the rats were injured but before sudden death. Electron microscopy, hematoxylin and eosin (HE) staining, TUNEL assays and immunohistochemistry techniques were used to observe the autophagy of the cells. Western blotting was used to analyze the expression of the autophagy-related factor Beclin-1 and the apoptosis-related factor caspase-3, and reverse transcription polymerase chain reaction (RT-PCR) was used to analyze the mRNA expression levels of the above proteins.

RESULTS: The locomotor scores of the rats in the saline group were significantly reduced, their Beclin-1 expression levels in neurons were decreased, and caspase-3 expression was increased. The hind limb locomotor scores of rats in the TUDCA groups were decreased, with no difference between the high- and low-dose groups. Beclin-1 expression in their neurons was increased, and caspase-3 expression was decreased; there was a significant difference when compared with the control group, while there was no significant difference between the high- and low-dose groups.

CONCLUSIONS: TUDCA significantly activates the neuronal autophagic expression in rats with acute spinal cord injury to inhibit the apoptosis of nerve cells; therefore, it has a protective effect on neurons.

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