[Mechanism of alpha-lipoic acid in treating TNBS-induced colitis in mice].

Objective: To investigate whether α-lipoic acid (ALA) regulates autophagy in the pathogenesis of colitis through the mammalian target of rapamycin (mTOR) signaling pathway. Methods: Balb/c mouse colitis model was induced with 2, 4, 6-trinitrobenzenesulfonic acid (TNBS). Male Balb/c mice (22-25 g) were divided into four groups: control group, ALA group, colitis group, and ALA treatment group, with 10 mice in each group. ALA was administered at a dose of 80 mg/kg once a day for 7 days. The colon weight index, the disease activity index (DAI) and the histologic degeneration score (HDS) of colon tissue in each group were calculated. The autophagy gene Beclin-1 mRNA level was detected by RT-PCR. The levels of mTOR, phosphorylated mTOR (p-mTOR), and Beclin-1 proteins were detected by Western blot. Results: Compared with the control group, there was no statistically significant difference in colon weight index in the ALA group[(9.21±0.57)vs(8.91±0.91)g/kg, P>0.05], but increased in the colitis group [(12.65±1.33)g/kg, P<0.05] and decreased in the ALA treatment group [(10.04±1.02)g/kg, P<0.05]; there were no significant differences in DAI or HDS in the ALA group, but significantly increased in the colitis group, and decreased in the ALA treatment group (all P<0.05). The Beclin-1 mRNA and protein levels showed no significant differences between the control and the ALA groups (1.00±0.12 vs 1.05±0.05, 1.00±0.11 vs 1.00±0.06). However, the expression of Beclin-1 was significantly decreased in the colitis group compared to the control group (0.51±0.07 vs 1.00±0.12, 0.52±0.07 vs 1.00±0.11, both P<0.05), but significantly increased in the ALA treatment group compared to the colitis group (1.75±0.09 vs 0.51±0.07, 1.82±0.14 vs 0.52±0.07, both P<0.05). The mTOR total protein levels were not significantly different among the four groups, but the p-mTOR level was significantly higher in the colitis group than in the control group (3.07±0.20 vs 1.00±0.07), and reduced in the ALA treatment group than in the colitis group (1.49±0.11 vs 3.07±0.20) (all P<0.05). Conclusion: ALA may improve the TNBS-induced colitis in mice by inhibiting the phosphorylation of mTOR to promote autophagy.