珠子参皂苷通过激活 PI3K/Akt通路对小鼠脑缺血再灌注损伤的保护作用研究

doi:10.12092/j.issn.1009-2501.2019.07.005

中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (7): 750-758.doi: 10.12092/j.issn.1009-2501.2019.07.005

珠子参皂苷通过激活 PI3K/Akt通路对小鼠脑缺血再灌注损伤的保护作用研究

段晋宁¹, 向常清², 钱爱红¹, 李进¹, 陈修全¹, 韩永峰¹, 黄娜¹, 范丽莉³

¹神农架林区人民医院内1科，神农架 442400，湖北；²三峡大学第二人民医院＆宜昌市第二人民医院重症医学科，宜昌 443000，湖北；³三峡大学附属仁和医院重症医学科，宜昌 443001，湖北

收稿日期:2019-01-02 修回日期:2019-06-02 出版日期:2019-07-26 发布日期:2019-07-29
通讯作者: 向常清，男，本科，主任医师，硕士研究生导师，研究方向：心脑血管疾病的基础与临床研究。 Tel: 0717-6211080 E-mail: 228339163@qq.com
作者简介:段晋宁，女，本科，主任医师，研究方向：心脑血管疾病基础与临床研究。 Tel: 0719-3337837 E-mail: 34418224@qq.com
基金资助:
神农架林区科学技术局项目(［2015］33-2)

Saponins from Rhizoma Panacis Majoris protect against cerebral ischemia and reperfusion injury through modulation of PI3K/Akt signaling pathway in mice

DUAN Jinning¹, XIANG Changqing², QIAN Aihong¹, LI Jin¹, CHEN Xiuquan¹, HAN Yongfeng¹, HUANG Na¹, FAN Lili³

¹Shennongjia Forest District People's Hospital, Shennongjia 442400, Hubei,China; ²The Second People's Hospital, China Three Gorges University &Yichang Second Hospital, Yichang 443000, Hubei,China; ³China Three Gorges University affiliated Renhe Hospital, Yichang 443001, Hubei, China

Received:2019-01-02 Revised:2019-06-02 Online:2019-07-26 Published:2019-07-29

摘要/Abstract

摘要：

目的: 研究珠子参皂苷对小鼠脑缺血再灌注损伤的保护作用及可能机制。方法:雄性昆明小鼠随机分为假手术组、模型组、珠子参皂苷(100 mg/kg)、珠子参皂苷(200 mg/kg)和尼莫地平组(2 mg/kg)。给药组灌胃给予相应的药物，假手术组和模型组灌胃给予同体积0.5%羧甲基纤维素钠溶液，每天1次，连续7 d。以上各组给药7 d后制作小鼠大脑中动脉闭塞模型，假手术组切开缝合不进行动脉阻塞，在缺血2 h再灌注24 h后进行神经功能缺损评分、脑水肿、梗死面积和脑组织形态学分析，血液中ROS、LDH、SOD、GSH-Px、CAT和MDA的水平检测，Western blot检测脑组织中p-PI3K、PI3K、p-Akt、Akt、Bcl-2、Bax、Cytochrome C、cleaved-caspase-9和cleaved-caspase-3蛋白表达。结果:珠子参皂苷(100和200 mg/kg)和尼莫地平(2 mg/kg)可显著改善脑缺血再灌注损伤小鼠神经功能缺损评分、脑水肿、梗死面积和脑组织形态学，降低血清ROS、LDH和MDA水平，升高SOD、GSH-Px、CAT活性，上调脑组织中p-PI3K、p-Akt、Bcl-2蛋白表达和升高Bcl-2/Bax比率，下调Bax、Cytochrome C、cleaved-caspase-9和cleaved-caspase-3蛋白表达。结论:珠子参皂苷对小鼠缺血再灌注损伤具有较好的保护作用，其作用机制可能与其激活PI3K/Akt通路和抑制线粒体介导的凋亡通路有关。

关键词: 珠子参皂苷, 脑缺血再灌注损伤, 氧化应激, PI3K/Akt和线粒体介导的凋亡通路

Abstract:

AIM: To study the protective effect and possible mechanism of saponins from Rhizoma Panacis Majoris (SRPM) on cerebral ischemia-reperfusion (I/R) injury in mice. METHODS: Male Kunming mice were randomly divided into sham operation group, model group, SRPM (100 mg/kg), SRPM (200 mg/kg) and nimodipine group (2 mg/kg). The drug groups were given corresponding drugs by gavage, while the sham operation group and the model group were given 0.5% sodium carboxymethyl cellulose solution by gavage once a day for 7 consecutive days. After 7 days of administration, the middle cerebral artery occlusion model was established in mice in the sham operation group. After 2 hours of ischemia and 24 hours of reperfusion, the neurological deficit score, brain edema, infarct area and brain histomorphology were analyzed. The levels of ROS, LDH, SOD, GSH-Px, CAT and MDA in blood were detected. The protein levels of p-PI3K, PI3K, p-Akt, Akt Bcl-2, Bax, cytochrome C, cleaved-caspase-9 and cleaved-caspase-3 in brain tissue were detected by Western blot. RESULTS:SRPM (100 and 200 mg/kg) and nimodipine (2 mg/kg) could significantly improve neurological deficit score, brain edema, infarct area and brain histomorphology in cerebral I/R injury mice, reduce the levels of ROS, LDH and MDA, increase SOD, GSH-Px, CAT activities in serum, up-regulate the protein expressions of p-PI3K, p-Akt, Bcl-2, and Bcl-2/Bax ratio, down-regulate the protein expressions of Bax, cytochrome C, cleaved-caspase-9 and cleaved-caspase-3. CONCLUSION: The protective effect of SRPM on I/R injury mice may be related to its activation of PI3K/Akt pathway and inhibition of mitochondrial-mediated apoptotic pathway.

Key words: Saponins from Rhizoma Panacis Majoris, cerebral ischemia and reperfusion injury, oxidative stress, PI3K/Akt signaling pathway and mitochondrial-mediated apoptotic pathway

中图分类号:

段晋宁, 向常清, 钱爱红, 李进, 陈修全, 韩永峰, 黄娜, 范丽莉. 珠子参皂苷通过激活 PI3K/Akt通路对小鼠脑缺血再灌注损伤的保护作用研究[J]. 中国临床药理学与治疗学, 2019, 24(7): 750-758.

DUAN Jinning, XIANG Changqing, QIAN Aihong, LI Jin, CHEN Xiuquan, HAN Yongfeng, HUANG Na, FAN Lili. Saponins from Rhizoma Panacis Majoris protect against cerebral ischemia and reperfusion injury through modulation of PI3K/Akt signaling pathway in mice[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(7): 750-758.

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珠子参皂苷通过激活 PI3K/Akt通路对小鼠脑缺血再灌注损伤的保护作用研究

Saponins from Rhizoma Panacis Majoris protect against cerebral ischemia and reperfusion injury through modulation of PI3K/Akt signaling pathway in mice

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