| 薛姗姗,周翠红,于 欢,赵洁玉,王化宁,彭正午.氟西汀对CUS大鼠抑郁样行为及海马内源性大麻素相关基因表达的调节作用[J].,2020,(7):1224-1229 |
| 氟西汀对CUS大鼠抑郁样行为及海马内源性大麻素相关基因表达的调节作用 |
| The Influence of Fluoxetine on the Depressive-like Behavior and the Expression of Endocannabinoid-Related Genes in the Hippocampus of CUS Rats |
| 投稿时间：2019-08-28 修订日期：2019-09-23 |
| DOI：10.13241/j.cnki.pmb.2020.07.005 |
| 中文关键词: 氟西汀 CUS 抑郁 内源性大麻素 |
| 英文关键词: Fluoxetine Chronic unpredictable stress Depressive Endocannabinoid |
| 基金项目:国家自然科学基金项目(81571309) |
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| 中文摘要: |
| 摘要 目的：探讨内源性大麻素1型受体（Cannabinoid receptor1，CB1R）、二酰基甘油脂肪酶（Diacylglycerol lipase alpha，DAGLα）和单酰甘油脂肪酶（Monoacylglycerol，MAGL）在氟西汀（Fluoxetine）改善慢性不可预见应激（Chronic unpredictable stress，CUS）大鼠抑郁样行为中的作用。方法：在本研究中，给予暴露于慢性不可预测应激（CUS）的大鼠腹腔注射氟西汀（10 mg/kg）或生理盐水治疗14天，最后一次腹腔注射结束24小时后评估抑郁样行为以及海马中CB1R，DAGLα和MAGL的表达。此外，通过注射慢病毒下调大鼠海马中CB1R和DAGLα的表达。病毒注射两周后，所有大鼠接受CUS刺激，然后腹腔注射10 mg/kg氟西汀或生理盐水14天。给药结束24小时后进行行为学及分子生物学检测。结果：（1）CUS组大鼠具有明显的抑郁样行为，包括旷场中心活动时间减少（P<0.05），糖水摄取量下降（P<0.05），强迫游泳不动时间增加（P<0.01）；氟西汀治疗可以缓解CUS大鼠的抑郁行为，与CUS组相比较，CUS + Flx组大鼠的糖水偏好和旷场中心活动时间增加（P<0.05，P<0.05），强迫游泳不动时间减少（P<0.05）；（2）CUS组大鼠海马的CB1R、DAGL?琢的表达下调（P<0.05），MAGL的表达上调（P<0.05）；氟西汀上调CUS大鼠海马的CB1R和DAGL?琢表达（P <0.05），下调了MAGL表达（P<0.05）；（3）病毒干预下调海马区的CB1R或DAGL?琢后，抑制了氟西汀的抗抑郁作用。结论：氟西汀可以通过调节CUS大鼠海马的内源性大麻素相关基因表达改善CUS大鼠的抑郁行为，发挥抗抑郁作用。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect of fluoxetine treatment on CUS rat's behavior and the expression of endocannabinoid system-related genes, including CB1R (Cannabinoid receptor1), DAGLα (Diacylglycerol) and MAGL (Monoacylglycerol) in the hippocampus. Methods: In the present study, rats exposed to chronic unpredictable stress (CUS) were treated with intraperitoneal injection of fluoxetine (10 mg/kg) or saline for 14 days, and depression-like behaviors and the expression of Cannabinoid receptor1 (CB1R), Diacylglycerol lipase alpha (DAGLα) and Monoacylglycerol (MAGL) in the hippocampus were evaluated twenty-four hours after the last intraperitoneal injection. In addition, we knocked-down CB1R and DAGLα in the hippocampus of rats by lentivirus injection.After the finally intervention, rats were experienced behavior test and then sacrificed and the expression of CB1R and DAGLα in hippocampus were determined. Results: (1) CUS group induced significant depression-like behaviors. Rats in CUS group showed significant less time in the center field (P<0.05), decreased sucrose preference (P<0.05) and increased immobility time in forced swim test (P<0.01). In comparison with Sham, the rat in CUS group showed significant decreased sucrose preference (P< 0.01) and less center time (P<0.05) in open filed test, but increased freezing time in forced swim test(P<0.05); as well as the reduction of the expression of CB1R and DAGLα, increasing the expression of MAGL in the hippocampus. (2) The expression of CB1R and DAGLα in hippocampus of CUS group was down-regulated (P<0.05), and the expression of MAGL was up-regulated (P<0.05). Fluoxetine treatment reversed depressive-like behaviors and increased the expression of CB1R and DAGLα (P<0.05), decreased the the expression of MAGL in the hippocampus of CUS rat (P<0.05); (3) Rats in shCB1R + CUS + Flx and shDAGLα + CUS + Flx groups showed decreased sucrose preference (P<0.05), less center time (P<0.05) in open filed test and increased freezing time in forced swim test (P<0.05) than rats in scramble + CUS + Flx group. Conclusion: Fluoxetine treatment reversed depressive-like behaviors in rats exposed to CUS paradigm and restored the level of CB1R, DAGLα and MAGL1in the hippocampus. |
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