基于微透析技术从Glu-GABA代谢通路探讨舒郁胶囊对经前烦躁障碍症肝气郁证的影响  

The mechanism of Shuyu capsules in treating premenstrual dysphoric disorder caused by liver qi depression based on microdialysis technology from the aspect of Glu-GABA metabolic pathway

作　　者：高兴笑 颜明 李帅 孙鹏[3] Gao Xingxiao;Yan Ming;Li Shuai;Sun Peng(Department of Pharmacy,Zaozhuang Hospital of Beijing University of Traditional Chinese Medicine,Zaozhuang 277000,China;Department of Infectious Diseases,Mining Group Central Hospital of Zaozhuang,Zaozhuang 277000,China;School of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250355,China)

机构地区：[1]北京中医药大学枣庄医院药学部,277000 [2]山东省枣庄矿业集团中心医院感染性疾病科,277000 [3]山东中医药大学药学院,济南250355

出　　处：《国际中医中药杂志》2021年第8期771-776,共6页International Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(81874419);山东省中医药科技项目(2020M126)。

摘　　要：目的基于谷氨酸/γ-氨基丁酸(Glu-GABA)代谢通路探讨舒郁胶囊对经前烦躁障碍症(premenstrual dysphoric disorder,PMDD)肝气郁证的作用。方法将36只旷场得分相近、动情周期规律的大鼠按随机数字表法分为空白组、模型组、氟西汀组、舒郁胶囊组、柴胡皂苷组和抑制剂组,每组6只。于动情周期确定后的第1个动情周期接受期进行海马立体定位手术。于第3、4个动情周期的非接受期进行束缚造模,并于造模第1天给药,氟西汀组灌胃氟西汀胶囊2.67 mg/kg,舒郁胶囊组灌胃舒郁胶囊0.408 g/kg,柴胡皂苷组灌胃柴胡皂苷0.72 mg/kg,1次/d,连续灌胃5 d;抑制剂组于造模最后1 d海马注射5 mmol/L谷氨酸脱羧酶抑制剂L-苹果酸20μl。给药结束后进行称重及旷场实验。采用微透析技术于大鼠第2、5个动情周期采集海马细胞外液,HPLC-FLD检测透析液中Glu、GABA含量。结果给药5 d后,与模型组比较,舒郁胶囊组、抑制剂组及氟西汀组大鼠体重升高(P<0.05),旷场实验总分降低(P<0.05);在第5个动情周期的接受期,舒郁胶囊组、抑制剂组Glu水平均降低(P<0.05);在第5个动情周期的非接受期,舒郁胶囊组、氟西汀组及柴胡皂苷组Glu水平升高,舒郁胶囊组、抑制剂组及氟西汀组GABA水平降低(P<0.05),舒郁胶囊组、氟西汀组及抑制剂组Glu/GABA[(1.49±0.13)、(1.32±0.33)、(3.92±0.79)比(0.35±0.48)]升高(P<0.05)。结论舒郁胶囊可通过抑制PMDD肝气郁证模型大鼠Glu-GABA代谢通路中谷氨酸脱羧酶,发挥治疗作用。Objective To explore the mechanism of premenstrual dysphoric disorder(PMDD)caused by liver-qi depression from the aspect of Glu-GABA metabolic pathways.Methods Thirty-six rats with similar open field scores and regular estrus cycles were divided into blank group,model group,fluoxetine group,Shuyu capsule group,saikosaponin group and inhibitor group according to the random number table method,with 6 rats in each group.Stereotactic hippocampus surgery was performed during the first estrous cycle reception period after the estrus cycle was determined.In the non-receiving period of the third and fourth estrus cycles,the restraint model was constructed,and from the first day of the modeling,rats of the fluoxetine group were given fluoxetine capsules 2.67 mg/kg,while rats of the Shuyu capsule group and saikosaponin group were given Shuyu capsules 0.408 g/kg and saikosaponin 0.72 mg/kg once a day for 5 consecutive days.Rats in the inhibitor group were injected with 20μl L-malic acid with 5 mmol/L concentration,which is an inhibitor of glutamate decarboxylase(GAD),in the hippocampus on the last day of modeling.After the administration,weighed the rats and carried out open field experiments.During the second and fivth estrus cycles of rats,the extracellular fluid of the hippocampus was collected by microdialysis technology,and the content of Glu and GABA in the dialysate was detected by HPLC-FLD.Results After 5 days of administration,compared with the model group,the body weight of rats in the Shuyu capsule group,the inhibitor group and the fluoxetine group increased(P<0.05),and the total score of the open field experiment decreased(P<0.05);compared with the model group,during the receiving period of the five estrus cycle,the Glu level of the Shuyu capsule group and the inhibitor group decreased(P<0.05);In the non-receiving period of the fifth estrus cycle,the Shuyu capsule group,Glu level of the fluoxetine group and the saikosaponin group increased,GABA level of Shuyu capsule group,inhibitor group and fluoxetine group d

关 键 词：谷氨酸 γ-氨基丁酸 微透析 经前期烦躁障碍症 舒郁胶囊 大鼠 

分 类 号：R285.5[医药卫生—中药学]