下丘脑-垂体-肾上腺轴紊乱对脊髓损伤大鼠抑郁样行为的影响及其机制

目的：观察下丘脑-垂体-肾上腺（HPA）轴紊乱对脊髓损伤（SCI）大鼠抑郁样行为和海马组织中Caspase-3蛋白表达水平的影响，并探讨其可能的作用机制。方法：清洁雄性SD大鼠40只随机分为正常组（12只）、假模组（12只）和SCI组（16只）。应用自制的打击器制备SCI模型。旷场实验检测各组大鼠自主活动总路程，蔗糖偏好实验检测各组大鼠蔗糖偏好百分比，强迫游泳实验检测各组大鼠强迫游泳不动时间，ELISA法检测各组大鼠血清促肾上腺皮质激素（ACTH）和皮质酮（CORT）水平。结果：旷场实验检测，不同时间点各组大鼠自主活动总路程比较差异有统计学意义（F=23.950，P=0.000）。蔗糖偏好实验检测，不同时间点各组大鼠蔗糖偏好百分比比较差异有统计学意义（F=11.99，P=0.001）；与基线时间点比较，损伤后第9和33天各组大鼠蔗糖偏好百分比升高（P<0.01）；与假模组比较，同一时间SCI组大鼠蔗糖偏好百分比降低（P<0.05）。强迫游泳实验检测，不同时间点各组大鼠强迫游泳不动时间比较差异有统计学意义（F=104.281，P=0.000），时间和组别之间存在交互作用（F=58.036，P=0.000）。ELISA法检测，不同时间点各组大鼠血清CORT水平比较差异有统计学意义（F=22.869，P=0.000）。时间和组别之间存在交互作用（F=7.753，P=0.000）；不同时间点各组大鼠血清ACTH水平比较差异有统计学意义（F=36.598，P=0.000），时间和组别之间存在交互作用（F=6.452，P=0.000）；各组大鼠海马组织中Caspase-3蛋白表达水平比较差异有统计学意义（F=169.937，P=0.000）；与正常组和假模组比较，SCI组大鼠海马组织中Caspase-3蛋白表达水平差异有统计学意义（P<0.01）。结论：SCI大鼠HPA轴功能亢进，致使海马组织中Caspase-3蛋白表达水平升高，导致SCI大鼠出现抑郁样行为表现，从而降低HPA轴的负反馈调节功能，促进SCI大鼠抑郁的发生发展。

Effect of hypothalamic-pituitary-adrenal axis disorder on depression-like behavior in rats with spinal cord injury and its mechanism

Objective: To observe the effect of hypothalamus pituitary adrenal axis(HPA) disorder on the depression-like behavior and the expression of Caspase-3 protein in hippocampus tissue of the spinal cord injury(SCI) rats, and to explore its possible mechanism. Methods: A total of 40 male SD rats were rardomly divided into normal group (12 rats), sham model group (12 rats) and SCI group (16 rats). The SCI model was made by using self-made impactor. Open field test was used to detect the total distance of locomotor activities, sucrose preference test was used to detect the percentages of sucrose preference, forced swimming test was used to detect the immobility time of forced swimming, and ELISA method was used to detect the serum adrenocorticotropic hormone(ACTH) and corticosterone(CORT) levels of the rats in various groups. Results: The Open field test results showed that there was a significant difference in the total distances of locomotor activities of the rats between various groups at different time points (F=23.950, P=0.000); the sucrose preference of showed that there was a significant difference in the percentages of sucrose preference of the rats between various groups at different time points (F=11.99, P=0.001); compared with the baseline time point, the difference of percentages of sucrose preference of the rats in various groups on the 9th and 33rd days were increased(P<0.01);compared wtih sham model group,the percentages of sucrose preference of the rats in SCI group were significantly decreased(P<0.05).The forced swimming test results showed that the differences of immobility time of forced swimming of the rats in various groups had a statistically significant difference(F=104.281, P=0.000) at different time points, and there was a interaction between time and groups(F=58.036, P=0.000). The ELISA results showed that there was a significant difference in the serum CORT level of the rats between various groups at different time points(F=22.869, P=0.000), and there was a interaction between time and groups (F=7.753, P=0.000). There was a significant difference in the serum ACTH levels of the rats between various groups at different time points(F=36.598, P=0.000), and there was a interaction between time and groups (F=6.452, P=0.000). The expression levels of Caspase-3 protein in hippocampus tissue of the rats in various groups had a statistically significant difference (F=169.937, P=0.000); compared with normal group and sham model group, the level of Caspase-3 protein in hippocampus tissue of the rats in SCI group had a statistically significant difference (P<0.01). Conclusion: The hyperfunction of HPA axis in the SCI rats leads to the increase of Caspase-3 protein expression in hippocampus tissue, which leads to the depression-like behavior in the SCI rats, thus reducing the negative feedback regulation function of HPA axis and promoting the occurrence and development of depression of the SCI rats.