芍药苷通过激活LKB1/ AMPK 信号通路对急性脑梗死大鼠神经损伤的保护作用
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作者单位:

1. 南阳医学高等专科学校,河南 南阳 473000;2. 河南省安阳市中医院神经外科,河南 安阳455000


Protective effect of paeoniflorin on nerve injury in rats with acute cerebral infarction by activating the LKB1/ AMPK signaling pathway
Author:
Affiliation:

1. Nanyang Medical College, Nanyang 473000, China. 2. Department of Neurosurgery, Henan Anyang Hospital of Traditional Chinese Medicine, Anyang 455000

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    摘要:

    目的 探讨芍药苷通过激活肝激酶B1(LKB1) /5’-磷酸腺苷激活的蛋白激酶(AMPK)信号通路对急性脑梗死大鼠神经损伤的保护作用。方法 通过线栓闭塞大鼠大脑中动脉建立急性脑梗死模型,随机分为模型组、芍药苷(10 mg/ kg)组、AMPK 抑制剂CC(0. 2 mg/ kg)组、芍药苷(10 mg/ kg)+ CC(0. 2 mg/ kg)组,每组12 只,另取12 只大鼠仅分离出颈总动脉与颈外动脉,不插线栓,设为假手术组,分组给药处理后,采用Morris 水迷宫实验评测大鼠认知功能;采用三苯基氯化四氮唑(TTC)染色检测各组大鼠脑梗死情况;采用TUNEL 染色测定各组大鼠海马神经元凋亡率;采用试剂盒测量各组大鼠血清炎性因子诱导型一氧化氮合酶(iNOS)与白细胞介素-1β(IL-1β)水平、脑组织过氧化氢酶(CAT)、活性氧(ROS)与丙二醛(MDA)含量;采用蛋白免疫印迹法检测各组大鼠脑组织凋亡相关蛋白B 淋巴细胞瘤-2(Bcl-2)、BCL2 相关X 蛋白(Bax)与LKB1/ AMPK 通路相关蛋白(p-LKB1/ LKB1、p-AMPK/AMPK)表达状况。结果 与假手术组相比,模型组大鼠跨越原平台次数、原平台象限内停留时间、脑组织CAT 含量、p-LKB1/ LKB1、p-AMPK/ AMPK、Bcl-2 表达水平显著降低( P < 0. 05),脑梗死面积、海马神经元凋亡率、血清iNOS 与IL-1β 水平、脑组织ROS 与MDA 含量、Bax 表达水平显著升高( P < 0. 05)。与模型组相比,芍药苷组大鼠跨越原平台次数、原平台象限内停留时间、脑组织CAT 含量、p-LKB1/ LKB1、p-AMPK/ AMPK、Bcl-2 表达水平显著升高( P < 0. 05),脑梗死面积、海马神经元凋亡率、血清iNOS 与IL-1β 水平、脑组织ROS 与MDA 含量、Bax 表达水平显著降低( P < 0. 05)。CC 可减轻芍药苷对大鼠脑梗死的保护作用。结论 芍药苷可能通过激活LKB1/ AMPK 信号通路,而阻止炎症发生发展,降低氧化应激水平,减轻大鼠脑组织梗死及海马神经元凋亡,改善其认知功能,起到保护神经的作用。CC 可减轻芍药苷对大鼠脑梗死的保护作用。

    Abstract:

    Objective To investigate the protective effect of paeoniflorin on nerve injury in rats with acute cerebral infarction by activating the liver kinase B1 ( LKB1) /5’-amp activated protein kinase (AMPK) signaling pathway. Methods An acute cerebral infarction model was established by occlusion of the middle cerebral artery in rats using sutures, and the rats were randomly divided into a Model group, Paeoniflorin (10 mg/ kg) group, AMPK inhibitor Compound C (CC) (0. 2 mg/ kg) group, and Paeoniflorin (10 mg/ kg) + CC (0. 2 mg/ kg) group, with 12 animals per group. In addition, 12 rats were separated from the common carotid artery and external carotid artery without the suture plug and used as the Sham group. After group administration, a Morris water maze test was used to evaluate the cognitive function of the rats. Triphenyltetrazolium chloride (TTC) staining was used to detect the cerebral infarction of rats in each group. TUNEL staining was used to determine the hippocampal neuron apoptosis rate of rats in each group. Kits were used to measure the levels of serum inflammatory factor inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β) levels, brain catalase (CAT), reactive oxygen species (ROS), and malondialdehyde (MDA) in the brain tissues of the rats. Western blotting was used to detect the expression of apoptosis-related proteins B-cell lymphoma-2 (Bcl-2), BCL2-associated X protein (Bax), and LKB1/ AMPK pathway related proteins (p-LKB1/ LKB1, p-LKB1/ LKB1, p-AMPK/ AMPK) in the brain tissues. Results Compared with the Sham operation group, the number of times crossing the original platform, residence time in the original platform quadrant, brain tissue CAT content, p-LKB1/ LKB1, p-AMPK/ AMPK, and Bcl-2 expression levels in the Model group were significantly less ( P < 0. 05), and the cerebral infarction area, hippocampal neuron apoptosis rate, serum iNOS and IL-1β levels, brain tissue ROS and MDA content, and Bax expression level were significantly greater ( P < 0. 05). Compared with the Model group, the number of times crossing the original platform, residence time in the original platform quadrant, brain tissue CAT content, p-LKB1/ LKB1, p-AMPK/ AMPK, and Bcl-2 expression levels in the Paeoniflorin group were significantly greater ( P < 0. 05), the cerebral infarction area, hippocampal neuron apoptosis rate, serum iNOS and IL-1β levels, brain tissue ROS and MDA contents, and Bax expression level were significantly less ( P < 0. 05). CC can reverse the protective effect of paeoniflorin in a rat cerebral infarction. Conclusions Paeoniflorin may activate the LKB1/ AMPK signal to prevent the occurrence and development of inflammation, reduce the oxidative stress level, reduce brain tissue infarction and hippocampal neuronal apoptosis in rats, improve cognitive function, and play a role in protecting nerves. CC can reduce the protective effect of paeoniflorin in a rat cerebral infarction. 【Keywords】 paeoniflorin; liver kinase B1/5’-amp activated protein kinase; acute cerebral infarction; nerve

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赵霞,薛娣,师少军.芍药苷通过激活LKB1/ AMPK 信号通路对急性脑梗死大鼠神经损伤的保护作用[J].中国实验动物学报,2022,30(5):671~678.

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  • 收稿日期:2021-11-09
  • 在线发布日期: 2023-04-13
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