To investigate the regulatory effect of hypoxic preconditioning (HPC) on the expression of mesencephalic astrocyte-derived neurotrophic factor (MANF) and endoplasmic reticulum stress (ERS) in rats with traumatic brain injury (TBI).

A total of 216 healthy male SD rats were randomly divided into four groups with different interventions: the blank control group (Con group, 12 rats) was raised routinely without any special treatment; the hypoxic preconditioning group (HPC group, 12 rats) received 3-day hypoxic preconditioning in a hypobaric oxygen chamber to simulate the plateau environment; the TBI group (96 rats) was only subjected to TBI model establishment via the free fall method; the hypoxic preconditioning plus TBI group (HPC+TBI group, 96 rats) was given 3-day hypoxic preconditioning first, followed by TBI model establishment; The TBI group and HPC+TBI group were further divided into 8 subgroups according to the sacrifice time after injury (1 h, 3 h, 6 h, 12 h, 1 d, 3 d, 7 d, 14 d), with 12 rats in each subgroup. The expression levels of MANF and C/EBP homologous protein in the four groups were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot.

Repeated measures ANOVA showed that qRT-PCR and Western blot detection results were consistent: the time effect, inter group effect, and interaction effect of MANF and CHOP expression in the four groups of rats were statistically significant (P<0.05). The expression of MANF in both TBI group and HPC+TBI group increased at 1 h after injury, reached its peak at 6 h, and then decreased, returning to baseline at 14 d; CHOP expression increased at 1 h after injury, peaked at 3 d, and then decreased, returning to baseline at 14 d; The differences between adjacent time points within the group were statistically significant (P<0.05). At 1 h, 3 h, 6 h, 12 h, 1 d, 3 d, and 7 d after injury, the expression of MANF and CHOP in the TBI group was higher than that in the Con group, and the expression in the HPC+TBI group was higher than that in the HPC group, with statistical significance (P<0.05). Compared with the TBI group, the TBI+HPC group showed upregulation of MANF expression and decrease of CHOP expression at 1 h, 3 h, 6 h, 12 h, 1 d, 3 d, and 7 d after injury, with statistical significance (P<0.05); there was no statistically significant difference in the expression of MANF and CHOP at 14 d after injury (P>0.05).

Hypoxic preconditioning can promote the up-regulation of MANF expression, reduce the expression level of CHOP by regulating ERS, and thereby alleviate cell apoptosis.