Huang Cai-Yun, Chen Na-Na, Zhou Fei, Zhang Hong-Mei, Yang Xiao-Rong
Department of Physiology, Shanxi Medical University, Key Laboratory of Cellular Physiology, Ministry of Education, Taiyuan 030001.
Department of Environmental Health, School of Public Health, Shanxi Medical University, Taiyuan 030001, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2022 Sep;38(5):458-463. doi: 10.12047/j.cjap.6306.2022.086.
To investigate the effects of silent information regulator 1 (SIRT1) in amygdala on depression-like behaviors in rats using chronic restraint stress (CRS) as a model of depression.
Sixty male SD rats were randomly divided into six groups (=10 per group): control group (Control), chronic restraint stress group (CRS), CRS + fluoxetine-treated group (CRS + FLU), CRS + saline-treated group (CRS + NaCl), CRS + SIRT1-overexpression group (CRS + AAV-SIRT1), and CRS + empty vector group (CRS + AAV-EGFP). Except for the control group, rats from the other groups were exposed to chronic restraint stress for 21 days. After the modeling, rats in fluoxetine-treated group and saline-treated group were, respectively, treated with fluoxetine (10 mg/kg) or saline (10 mg/kg) by gavage every day for 3 weeks; AAV-SIRT1 or AAV-EGFP was, respectively, stereotaxically injected into the amygdala of rats in SIRT1-overexpression group and empty vector group, and the virus was expressed for 3 weeks. Rats in normal control group and CRS model group were not given any drug treatment. The depression-like behaviors of rats in each group were evaluated by sugar preference test (SPT), open field test (OFT) and forced swimming test (FST). SIRT1 expression in amygdala of rats was assessed by using immunoblot blotting. The number of SIRT1-positive cells in amygdala of rats was detected by immunofluorescence technique.
Compared with the normal control group, the level of SIRT1 protein and the number of SIRT1 cells in amygdala of the CRS-exposed rats were decreased significantly (＜0.01), and CRS-exposed rats showed a significant decrease in sucrose preference (＜0.01), less total horizontal distance (＜0.01) and less time entered the center field (＜0.01) in the OFT, a significant increase in the immobility time of the FST (＜0.01). Fluoxetine treatment (＜0.05, ＜0.01) or SIRT1 overexpression (＜0.01) partially reversed the down-regulation of SIRT1 protein and SIRT1 cells in amygdala of CRS-exposed rats and significantly improved the depression-like behaviors of CRS rats.
Fluoxetine treatment partially reversed the down-regulation of SIRT1 level and the number of SIRT1 in CRS rats, and significantly improved the depression-like behaviors. The antidepressant effect of fluoxetine treatment may be related to the up-regulation of SIRT1 in the amygdala of CRS-exposed rats.
以慢性束缚应激（CRS）作为抑郁症模型，研究杏仁核中沉默信息调节因子1（SIRT1）对大鼠抑郁样行为的影响。
将60只雄性SD大鼠随机分为6组（每组 = 10只）：对照组（Control）、慢性束缚应激组（CRS）、CRS + 氟西汀治疗组（CRS + FLU）、CRS + 生理盐水治疗组（CRS + NaCl）、CRS + SIRT1过表达组（CRS + AAV - SIRT1）和CRS + 空载体组（CRS + AAV - EGFP）。除对照组外，其他组大鼠接受21天的慢性束缚应激。造模后，氟西汀治疗组和生理盐水治疗组大鼠分别每天灌胃给予氟西汀（10 mg/kg）或生理盐水（10 mg/kg），持续3周；将AAV - SIRT1或AAV - EGFP分别立体定向注射到SIRT1过表达组和空载体组大鼠的杏仁核中，病毒表达3周。正常对照组和CRS模型组大鼠不给予任何药物治疗。通过糖水偏好试验（SPT）、旷场试验（OFT）和强迫游泳试验（FST）评估各组大鼠的抑郁样行为。采用免疫印迹法评估大鼠杏仁核中SIRT1的表达。通过免疫荧光技术检测大鼠杏仁核中SIRT1阳性细胞的数量。
与正常对照组相比，CRS大鼠杏仁核中SIRT1蛋白水平和SIRT1细胞数量显著降低（＜0.01），CRS大鼠在SPT中蔗糖偏好显著降低（＜0.01），在OFT中总水平移动距离显著减少（＜0.01）且进入中央区域的时间显著减少（＜0.01），在FST中不动时间显著增加（＜0.01）。氟西汀治疗（＜0.05，＜0.01）或SIRT1过表达（＜0.01）部分逆转了CRS大鼠杏仁核中SIRT1蛋白和SIRT1细胞的下调，并显著改善了CRS大鼠的抑郁样行为。
氟西汀治疗部分逆转了CRS大鼠中SIRT1水平和SIRT1数量的下调，并显著改善了抑郁样行为。氟西汀治疗的抗抑郁作用可能与上调CRS大鼠杏仁核中的SIRT1有关。
