目的 研究术后疲劳综合征(POFS)大鼠海马内炎症因子及经典炎症通路变化,探讨POFS的中枢发生机制,并考察人参皂苷Rb₁对中枢疲劳的干预作用。方法 将96只SD大鼠随机分为对照组、POFS模型组(POFS组)和人参皂苷Rb₁干预组(人参皂苷Rb₁组),每组再按时间点分为术后1、3、5、7 d 4个亚组。术后对应时间点进行旷场实验,实时荧光定量PCR检测大鼠海马炎症因子的mRNA表达;Western blotting检测磷酸化p38(p-p38)、核因子κB/p65(NF-κB/p65)蛋白表达;免疫组化法检测海马内p-p38蛋白表达;免疫荧光法检测海马内NF-κB/p65蛋白核内外分布。结果 术后1、3 d,与对照组比较,POFS组大鼠运动距离减少(P < 0.01),休息时间增加(P < 0.05);中枢内炎症因子水平升高(P < 0.05);p-p38蛋白表达也增加(P < 0.05),(NF-κB/p65胞核)/(NF-κB/p65胞浆) 增加(P < 0.05);人参皂苷Rb₁组与POFS组比较,术后1、5 d,大鼠休息时间明显缩短(P < 0.05);术后1、3 d,大鼠运动距离增加(P < 0.01),炎症因子表达下降(P < 0.05),(NF-κB/p65胞核)/(NF-κB/p65胞浆) 明显减少(P < 0.05);术后3、5、7 d p-p38蛋白表达也降低(P < 0.05)。免疫组化、免疫荧光结果与Western blotting结果相同。结论 POFS大鼠海马内炎症因子表达升高,经典炎症通路激活,人参皂苷Rb₁可通过抗炎作用来改善POFS大鼠的中枢疲劳。

Objective To explore the inflammatory factor and inflammation signal pathway in hippocampus of postoperative fatigue syndrome (POFS) rats, and to investigate the central mechanism of POFS and the anti-fatigue effect of ginsenoside Rb₁. Methods Ninety-six male SD rats were randomly divided into control, POFS, and ginsengoside Rb₁ intervention groups (ginsengoside Rb₁ groups), and each group was divided into subgroups by postoperative 1, 3, 5, and 7 d. The fatigue was assessed with open field test. The mRNA levels of inflammatory cytokines in hippocampus were measured by real-time quantitative PCR. The activation of p38MAPK enzyme was examined by Western blotting and immunohistochemisty. The translocation of NF-κB/p65 in nuclear was measured by Western blotting and immunohistofluorescence. Results On postoperative day 1 and day 3, compared with the control group, the journey of rats in the POFS group declined (P < 0.01), while resting time increased (P < 0.01), the level of inflammation cytokines added, the expression of p-p38MAPK protein was enhanced and the ratio of NF-κB/p65 cytoplasm/NF-κB/p65/nuclear was also elevated (P < 0.05). Compared with the POFS group, the resting time of rats decreased (P < 0.05) on postoperative day 1 and day 5.On day 1 and day 3 after surgery, the journey of rats was enhanced (P < 0.01), the level of inflammation cytokines was declined and the ratio of NF-κB/p65 cytoplasm/NF-κB/p65/nuclear was decreased (P < 0.05). The levels of p-p38MAPK in postoperative day 3, day 5, and day 7 were also declined (P < 0.05). The results of immunohistochemisty and immunohistofluorescence were accordance with Western blotting. Conclusion The inflammatory cytokine in hippocampus of POFS rats is increased and the inflammation signal pathway is activated. Ginsenoside Rb₁ has some improvement effects on central fatigue in POFS rats.

国家自然科学基金资助项目(81171857);浙江省自然科学基金资助项目(LZ12H07001);浙江省卫生部共建项目(201231118)