三七叶总皂苷抗老年焦虑症的作用及机制研究

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摘要目的探讨三七叶总皂苷（tSPNL）抗老年焦虑症的作用及其作用机制。方法 12月龄雄性小鼠75只按照随机数字表法分为群养（n = 15，正常对照组）和孤养（n = 60），4周后孤养动物随机分为模型组（溶媒）、地西泮（BDZ）组、tSPNL高剂量组（500 mg/kg tSPNL）及tSPNL低剂量组（100 mg/kg tSPNL），每天灌胃给药1次，连续给药14 d后用高架十字迷宫（EPM）进行行为学测定；行为学实验结束后，采用酶联免疫吸附法检测海马内γ-氨基丁酸（GABA）、脑源性神经营养因子（BDNF）的含量。另取12月龄雄性小鼠135只孤养，4周后随机分为模型组（溶媒）、BDZ组、氟西汀组、tSPNL高剂量组，每天灌胃给药1次，连续灌胃给药14 d后脑室内注射BDNF受体TrkB阻断剂K252a、GABAA受体阻断剂荷包牡丹碱（Bic），1 h后EPM进行行为学检测。结果与模型组比较，tSPNL高剂量组小鼠开臂时间百分比（OT%）增加，差异有高度统计学意义（P < 0.01）；海马BDNF、GABA水平增加，差异有统计学意义（P < 0.05或P < 0.01）。tSPNL组脑室内同时注射K252a及Bic后OT%降低，差异有统计学意义（P < 0.05）。结论 tSPNL具有抗老年焦虑症的作用，其抗焦虑作用与BDNF-GABA信号通路有关，可能通过增加BDNF水平改善GABA能神经的可塑性，从而降低老龄小鼠焦虑易感性。

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	杜瑶1
	2 李欣1 张桂仙1 袁娅金1 周宁娜1

关键词 ：老年焦虑症, 三七叶总皂苷, BDNF-GABA信号通路, &gamma, -氨基丁酸能神经可塑性

Abstract：Objective To explore the effect and mechanism of total saponins of Panax notoginseng leaves (tSPNL) on late-life anxiety. Methods Fifty aging male mice (12 months) were reared in group (n = 15, normal control group) or isolation (n = 60) according to the random number table method. After 4 weeks, the isolated rearing animal were then randomly divided into model group (vehicle), Diazepam (BDZ) group, tSPNL 500 group (500 mg/kg tSPNL) and tSPNL 100 group (100 mg/kg tSPNL). All mice were intragastrically administered desired compounds once a day for consecutive 14 days. The anxiety-like behaviors were evaluated by elevated plus maze (EPM), and levels of GABA and BDNF in hippocampus were determined by enzyme linked immunosorbent assay after the behavior test. In another set, aging male mice (n = 135) were rearing isolated for 4 weeks and were then randomly divided into model (vehicle), BDZ group, fluoxetine group, tSPNL 500 group. After administration of desired compounds intragastrically once a day for 14 days, animals underwent intraventricular injection of either BDNF receptor TrkB antagonist K252a or GABAA receptor antagonist Bicuculline (Bic), and the anxiety-like behaviors were measured by EPM 1 hour later. Results Compared with model group, the percentage of open arm time (OT%) increased significantly in tSPNL 500 group (P < 0.01), and the levels of BDNF and GABA also increased in hippocampus significantly (P < 0.05 or P < 0.01). After intraventricular injection of K252a and Bic, OT% in tSPNL 500 group decreased significantly (P < 0.05). Conclusion tSPNL can alleviate the anxiety-like behaviors in aging mice, and the mechanism is involved in BDNF-GABA signaling pathway, which may restore the GABAergic plasticity by increasing BDNF levels, thereby reducing the anxiety susceptibility of aging mice.

Key words： Late-life anxiety Total saponins of Panax notoginseng leaves GABA-BDNF signaling pathway GABAergic plasticity

基金资助:国家自然科学基金资助项目（81260649）；
云南省中医药领军人才项目。

通讯作者: 周宁娜（1971-），女，硕士，教授，硕士生导师；研究方向：中药药理与应用。

作者简介: 杜瑶（1992-），女，硕士，药师；研究方向：中药制剂研发。

引用本文:

杜瑶1,2 李欣1 张桂仙1 袁娅金1 周宁娜1. 三七叶总皂苷抗老年焦虑症的作用及机制研究[J]. 中国医药导报, 2019, 16(22): 7-11.
DU Yao1,2 LI Xin1 ZHANG Guixian1 YUAN Yajin1 ZHOU Ningna1. Study on the effect and mechanism of total saponins of panax notoginseng on late-life anxiety. 中国医药导报, 2019, 16(22): 7-11.

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http://www.yiyaodaobao.com.cn/CN/ 或 http://www.yiyaodaobao.com.cn/CN/Y2019/V16/I22/7

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