Abstract
Objective: To explore themechanism of tauroursodeoxycholic acid- (TUDCA) mediated neuronal protection after acute spinal cord injury (ASCI) in rats. Methods: ASCI rat model was established following modified Allen's weight-drop method and these rats were assigned to sham group (received sham operation), model group (ASCI rats), TUDCA group (ASCI rats received TUDCA treatment), MK2206 group (ASCI rats received AKT inhibitor MK2206 orally) and TUDCA + MK2206 group. Motor function of rats was evaluated using Basso Beattie Bresnahan (BBB) method. Hematoxylin-eosin (H&E) staining was used to detect histopathologic changes in the spinal cord and TUNEL fluorescence staining was used to check apoptosis. Real time fluorescence quantitative polymerase chain reaction (qRT-PCR) and western blot were employed to detect the production of AKT pathway related factors, apoptosis related factors (Bax, Bcl-2, caspase-3), autophagy related factor Beclin-1 and endoplasmic reticulum (ER) stress related factors (IRE1, Chop, ATF6) in spinal cord of rats. Results: Compared to the rats in the sham group, rats in ASCI group had decreased BBB scores (P<0.05), more significant tissue edema, structural cavity and apoptosis. Compared to rats in sham group, AKT pathway was inactivated in ASCI rats and was activated by TUDCA treatment (P<0.05). Compared to sham group, expressions of ER stress-related factors were increased, apoptosis was largely induced in other four groups, and expression of Beclin-1 was increased in the model group (P<0.05). TUDCA increased the expression of Beclin-1 and Bcl-2, and inhibited the expression of Bax, Caspase-3, and ER stress-related factors, thus suppressing apoptosis (P<0.05). Treatment by MK2206 had contrary effects and protective effects of TUDCA on ASCI rats could be counteracted by MK2206. Conclusion: TUDCA can significantly improve the neural damage, enhance neuron autophagy, alleviate ER stress, and inhibit apoptosis in ASCI rats, by activating the AKT signaling pathway.