中国科学院心理研究所机构知识库

为探讨芳樟精油的抗抑郁作用及其对炎症因子和核转录因子E2 相关因子 2 (Nrf2)/血红素加氧酶-1（HO-1）通路的调控机制，采用腹腔注射脂多糖（LPS）建立小鼠抑郁模型，利用旷场实验、高架十字迷宫实验和强迫游泳实验进行行为学测试；通过Western blot和qRT-PCR方法检测小鼠海马组织中Nrf2/HO-1通路蛋白表达水平变化， 用酶联免疫吸附检测（ELISA）法检测血清中炎症因子肿瘤坏死因子-α (TNF-α)、白细胞介素(IL)-6和IL-1β的含量变化，并通过Tunel染色检测小鼠脑组织细胞凋亡情况的变化；结果表明，与空白对照组相比，模型组小鼠旷场中心区运动距离、旷场中心的停留时间和中心区域的进入次数显著减少，高架十字迷宫实验中小鼠进入开臂的时间百分比（OT%）和进入开臂的次数百分比（OE%）显著减少，强迫游泳实验小鼠不动时间显著延长；而相较模型组，给予芳樟精油治疗后，小鼠在旷场实验中心区域运动距离显著增加，在旷场中心区域的停留时间显著增加，旷场中心区域的进入次数显著增加，高架十字迷宫小鼠进入开臂的OT%和OE%显著增加，强迫游泳实验中小鼠不动时间显著减少；此外，模型组小鼠的Nrf2、HO-1蛋白表达水平显著下降，TNF-α、IL-6和IL-1β炎症因子显著升高；给予芳樟精油治疗后能显著提高抑郁模型小鼠Nrf2、HO-1蛋白表达水平，并显著降低炎性因子TNF-α、IL-6和IL-1β。Tunel染色检测结果显示，给予芳樟精油治疗后，小鼠脑组织细胞凋亡率显著下降。综上所述，芳樟精油能有效改善小鼠的抑郁样行为，其机制可能与其参与调控Nrf2/HO-1信号通路，上调Nrf2、HO-1蛋白表达水平并阻止海马炎症损伤有关，这一发现为芳樟精油及芳香疗法在抑郁症中的治疗及应用提供了实证支持。

Abstract This study aims to investigate the essential oil (EOL) of Cinnamomum camphora regarding its anti-depression effect and mechanism in regulating inflammatory cytokines and the nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) pathway. A mouse model of depression was established by intraperitoneal injection of lipopolysaccharide (LPS). Open field, elevated plus maze, and forced swimming tests were carried out to examine mouse behaviors. Western blot and qRT-PCR were employed to determine the expression of proteins in the Nrf2/HO-1 pathway in the hippocampus. The levels of tumor necrosis factor (TNF)-α, interleukin (IL）-6, and IL-1β in the serum were measured by enzyme-linked immunosorbent assay (ELISA). The changes of apoptosis in mouse brain were detected by Tunel staining. Compared with the blank control group, the model group showed shortened distance travelled and time spent in the central zone and reduced number of entries in the central zone in the open field test. In the elevated plus maze test, the model group showed reduced open arm time (OT%) and open arm entries (OE%). In the force swimming test, the model group showed extended duration of immobility compared with the blank control group. Compared with the model group, the treatment with EOL significantly increased the distance travelled and time spent in the central zone and increased the number of entries in the central zone in the open field test. In addition, EOL significantly increased the OT% and OE% in the elevated plus maze and shortened the immobility duration in the forced swimming test. The model group showed lower expression levels of Nrf2 and HO-1 and higher levels of TNF-a, IL-6, and IL-1/β than the blank control group. Compared with the model group, the treatment with EOL up-regulated the expression levels of Nrf2 and HO-1 and lowered the levels of TNF-a, IL-6, and IL-1/β3. The Tunel staining results showed that the apoptosis rate in the brain tissue of mice decreased significantly after the treatment with EOI. To sum up, EOL can mitigate the depression-like behaviors of mice by up-regulating the expression of Nrf2 and HO-1 and preventing hippocampal inflammatory damage. The findings provide empirical support for the application of EOL and aromatherapy in the treatment of depression.

国家自然利学基金项目(82073971);中国利学院心理研究所自主部署课题(E2CX4115CX)