探讨缺氧预处理（HPC）对创伤性颅脑损伤（TBI）大鼠中脑星形胶质细胞源性神经营养因子（MANF）的表达及内质网应激（ERS）产生的调控作用。

216只健康雄性SD大鼠，采用随机数字表法分为4组：空白对照组（Con组，12只）仅常规饲养不做特殊处理；缺氧预处理组（HPC组，12只）予低压氧舱模拟高原环境行3 d的HPC；创伤性颅脑损伤组（TBI组，96只）仅构建自由落体法TBI模型，缺氧预处理+创伤性颅脑损伤组（HPC+TBI组，96只）先予以3 d的HPC再构建TBI模型；TBI组与HPC+TBI组依据伤后处死时间进一步划分为1 h、3 h、6 h、12 h、1 d、3 d、7 d、14 d 8个亚组，每个亚组12只。采用qRT-PCR和Western blot法测定4组大鼠MANF、C/EBP同源蛋白（CHOP）的表达变化。

重复测量方差分析显示，qRT-PCR和Western blot检测结果一致：4组大鼠的MANF和CHOP表达的时间效应、组间效应及交互效应差异均有统计学意义（P<0.05）。TBI组与HPC+TBI组的MANF表达均于损伤后1 h升高，6 h达峰值，之后开始下降，14 d恢复基线；CHOP表达均于损伤后1 h升高，3 d达峰值，之后开始下降，14 d时恢复基线；组内相邻时间点差异均有统计学意义（P<0.05）。损伤后1 h、3 h、6 h、12 h、1 d、3 d、7 d，TBI组的MANF与CHOP表达均高于Con组，HPC+TBI组均高于HPC组，差异均有统计学意义（P<0.05）。与TBI组比较，TBI+HPC组损伤后1 h、3 h、6 h、12 h、1 d、3 d、7 d的MANF表达上调、CHOP表达下降，差异有统计学意义（P<0.05）；损伤后14 d的MANF与CHOP表达差异均无统计学意义（P>0.05）。

HPC能够促进MANF表达上调，通过调控ERS来降低CHOP的表达水平，进而减轻细胞凋亡现象。

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.