木兰花碱减轻慢性应激小鼠抑郁样行为及对脑部LSD1组蛋白修饰的影响  

The effects of magnoflorine on depression-like behavior in chronic unpredictable mild stress mice and its effect on LSD1 modification in brain

作　　者：曹冰雁 刘艺洁[2] 武莉莉[2] 费乔曼 杨冰[2] 张玲[2] 乔卫 CAO Bing-yan;LIU Yi-jie;WU Li-li;FEI Qiao-man;YANG Bing;ZHANG Ling;QIAO Wei(School of Pharmacy,Tianjin Medical University,Laboratory on Technologies Enabling Development of Clinical Therapeuticsand Diagnostics (Theranostics),Tianjin 300070,China;School of Basic Medical Sciences,Tianjin Medical University)

机构地区：[1]天津医科大学药学院天津市临床药物关键技术重点实验室,300070 [2]天津医科大学基础医学院

出　　处：《天津医药》2019年第4期391-394,I0002,共5页Tianjin Medical Journal

基　　金：国家自然科学基金资助项目(81173530);天津市自然科学基金重点项目(17JCZDJC33200)

摘　　要：目的探索木兰花碱对慢性不可预见性温和应激所致抑郁小鼠行为学的影响机制。方法将ICR小鼠随机分为正常对照组(control组)、抑郁模型组(PG组)、木兰花碱高剂量组(MH组)和木兰花碱低剂量组(ML组)。采用慢性不可预见性温和刺激方法建立抑郁小鼠模型,检测各组小鼠行为学的变化,并用实时定量PCR、Western blot检测小鼠脑部赖氨酸特异性组蛋白去甲基化酶1(LSD1)mRNA及蛋白表达水平的变化。免疫组化染色法检测小鼠脑部LSD1阳性细胞数量。结果木兰花碱在行为学上改善了小鼠的抑郁状况,与PG组相比,MH组和ML组悬尾不动时间、强迫游泳不动时间明显缩短(P<0.05)。实时定量PCR及Western blot结果显示,与control组相比,PG组LSD1mRNA表达差异无统计学意义,蛋白表达明显降低(P<0.05),ML组LSD1 mRNA和蛋白表达明显升高(P<0.05);与PG组相比,ML组LSD1 mRNA和蛋白表达明显升高(P<0.05)。免疫组化结果显示,与control组相比,PG组小鼠脑部LSD1阳性细胞数量减少,而ML组较PG组增加。结论在木兰花碱治疗抑郁小鼠的过程中,LSD1可能起到了重要的调节作用。Objective To explore the mechanism of the effect of magnoflorine on the behavior of mice with depression caused by chronic unpredictable mild stress.Methods The ICR mice were randomly divided into normal control group(control group),positive depression group(PG group),high dose of magnoflorine group(MH group)and low dose of magnoflorine group(ML group).Depression mouse model was established by chronic unpredictable mild stress method.The behavioral changes of mice were detected.The expressions of lysine specific demethylase 1(LSD1)mRNA and protein in brain of mice were detected by real-time quantitative PCR,Western blot assay and immunohistochemistry.Results Magnoflorine improved the depression in mice.Compared with the PG group,the motionless time of tail suspension and motionless time of forced swimming were significantly shorter in the MH group and the ML group(P<0.05).Real-time quantitative PCR and Western blot assay showed that there was no significant difference in LSD1 mRNA expression between the PG group and the control group.The protein expression was significantly decreased(P<0.05).The expressions of LSD1 mRNA and protein were significantly increased in the ML group compared with those of control group(P<0.05).Compared with the PG group,the expressions of LSD1 mRNA and protein were significantly increased in the ML group(P<0.05).The results of immunohistochemistry showed that the number of positive cells in brain was decreased in the PG group compared with that of the control group,while it was increased in the ML group compared with that of PG group.Conclusion LSD1 may play an important role in the treatment with magnoflorine for depressed mice.

关 键 词：抑郁 慢性不可预见性温和刺激 木兰花碱 赖氨酸特异性组蛋白去甲基化酶1 

分 类 号：R285.5[医药卫生—中药学]