丹皮酚对PMDD肝气逆证模型大鼠焦虑样行为及其神经内分泌功能的影响  

Effects of Paeonol on Anxiety Like Behavior and Neuroendocrine Function in PMDD Rats with Liver Qi Inverse Syndrome

作　　者：邢影 李亚琼 刘坤 张浩 胡明会 李自发[2] 耿希文 魏盛[2] Xing Ying;Li Yaqiong;Liu Kun;Zhang Hao;Hu Minghui;Li Zifa;Geng Xiwen;Wei Sheng(College of Traditional Chinese Medicine,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Experimental Center of Shandong University of Traditional Chinese Medicine,Jinan 250355,China)

机构地区：[1]山东中医药大学中医学院,济南250355 [2]山东中医药大学实验中心,济南250355

出　　处：《世界科学技术-中医药现代化》2022年第9期3570-3579,共10页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委员会常规面上项目(81974553):从中枢PAG区对ALLO波动敏感性探讨中药舒郁胶囊对PMDD肝气郁证干预机制,负责人:魏盛;国家自然科学基金委员会青年科学基金项目(82004078):PINK1/Parkin通路介导的线粒体自噬在帕金森病肾精亏虚证及地黄饮子治疗中的作用机制研究,负责人:耿希文;山东省自然科学基金委员会面上项目(ZR2019MH053):从CORT-BDNF-ERK1/2信号级联介导的海马损伤探讨母鼠孕前肝气郁结影响子代行为表型的机制,负责人:魏盛

摘　　要：目的观察丹皮酚对经前烦躁障碍症(Premenstrual Dysphoric Disorder,PMDD)肝气逆证模型大鼠行为学和孕酮(P)、四氢孕酮(ALLO)、海马脑区GABAARα4 mRNA和蛋白表达的影响、以探讨其作用机制。方法将大鼠分为正常组(Control)、模型组(Model)、模型+丹皮酚低剂量组(Model+6.05)、模型+丹皮酚中剂量组(Model+12.11)、模型+丹皮酚高剂量组(Model+24.23)、模型+氟西汀组(Model+FLX),运用攻击行为测试(RIT)、旷场实验(OFT)、高架十字迷宫实验(EPM)等检测大鼠的焦虑样行为,ELISA检测血清及海马P、ALLO的含量,通过免疫荧光和PCR检测海马脑区GABAARα4的蛋白定位和mRNA的表达。结果与正常组相比,模型组OFT的Center distance(中央区运动路程)、Center time(中央区停留时间)显著下降(P<0.05,P<0.001),相比模型组,氟西汀组OFT的Center time(中央区停留时间)显著上升(P<0.05);与模型组相比,氟西汀组和丹皮酚中剂量组进入EPM开放臂次数和时间百分比明显上升(P<0.05,P<0.01,P<0.05,P<0.001);与模型组相比,丹皮酚中剂量组血清中P、ALLO的含量显著增加(P<0.001,P<0.01),丹皮酚高剂量组血清中ALLO含量明显升高(P<0.05);与模型组相比,丹皮酚中剂量组海马脑区中P含量显著升高(P<0.01);各给药组海马脑区中ALLO含量明显增加(P<0.01、P<0.001、P<0.0001、P<0.001);与正常组相比,模型组GABAARα4蛋白含量显著性降低(P<0.05),相比模型组,丹皮酚低剂量组和丹皮酚中剂量组显著性降低(P<0.05,P<0.05);与正常组相比,模型组海马脑区内GABAARα4 mRNA表达显著性升高(P<0.01)。结论丹皮酚可有效改善PMDD肝气逆证大鼠焦虑样行为,且中剂量用药可发挥更明显的疗效,其作用机制可能与纠正P、ALLO、GABAARα4有关。Objective In order to investigate the impact of Paeonol on the behavior of rats and expression of Progesterone(P),Allopregnanolone(ALLO),and GABAARα4 mRNA and protein in hippocampus of the liver-Qi invasion model rats with PMDD to explore its mechanism.Methods Divided the rats into six group including one normal group,one model group and other model groups,which were treated by Paeonol low-dose,Paeonol medium-dose,Paeonol high-dose and fluoxetine.Behavioral tests such as Resident Intruder Test(RIT),Open Field Test(OFT)and Elevated Plus Maze(EPM)were used to evaluation the anxiety-like behaviors of rats.The levels of serum and hippocampal P,ALLO were measured by ELISA,and the protein localization and mRNA expression of GABAARα4 in the hippocampal brain region were tested by immunofluorescence and PCR.Results The movement distance and residence time in the central area of the OFT in the model group were significantly decreased(P<0.05,P<0.001)compared to the normal group;In OFT,the residence time in the central area of fluoxetine group was significantly higher(P<0.05)than model group;In addition,along with the Paeonol medium-dose group,the frequency to enter the EPM open arm and the percentage of time to enter it increased significantly(P<0.05,P<0.01,P<0.05,P<0.001);The contents ALLO in the serum increased significantly(P<0.001,P<0.05)of both Paeonol medium-dose and high-dose group compared to the model group;But only in the Paeonol medium-dose group that the contents of P in both serum and hippocampus increased significantly(P<0.001,P<0.01);In addition to the model group,the ALLO contents in the hippocampus were significantly increased(P<0.01,P<0.001,P<0.0001,P<0.001);the GABAARα4 protein content of the model group was higher(P<0.05)than the normal group;the protein content of both Paeonol low-dose and medium-dose group were significantly less(P<0.05,P<0.05)than the model group;GABAARα4 mRNA expression in the hippocampal brain region was significantly higher in the model group than in the normal group(P<0.01).C

关 键 词：丹皮酚 PMDD肝气逆证 P ALLO GABA GABAARα4 

分 类 号：R285.5[医药卫生—中药学]