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、DAGLα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DAGLα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DAGLα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。
Objective: To investigate the effect of fluoxetine treatment on CUS rat’s behavior and the expression of endocannabinoid system-related genes, including CB1 R(Cannabinoid receptor1), DAGL α(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(CB1 R),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 CB1 R 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 CB1 R 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 CB1 R and DAGLα, increasing the expression of MAGL in the hippocampus.(2) The expression of CB1 R 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 CB1 R and DAGLα(P<0.05), decreased the the expression of MAGL in the hippocampus of CUS rat(P<0.05);(3) Rats in shCB1 R + 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 s
作者
薛姗姗
周翠红
于欢
赵洁玉
王化宁
彭正午
XUE Shan-shan;ZHOU Cui-hong;YU Huan;ZHAO Jie-yu;WANG Hua-ning;PENG Zheng-wu(Department of Psychosomatic,Xijing Hospital,Fourth Military Medical University,Xi'an,Shaanxi,710032,China)
出处
《现代生物医学进展》
CAS
2020年第7期1224-1229,1252,共7页
Progress in Modern Biomedicine
基金
国家自然科学基金项目(81571309)。
关键词
氟西汀
CUS
抑郁
内源性大麻素
Fluoxetine
Chronic unpredictable stress
Depressive
Endocannabinoid
