赤芍总苷减轻脑缺血/再灌注模型大鼠脑损伤

doi:10.16352/j.issn.1001-6325.2025.01.0025

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (1): 25-30.doi: 10.16352/j.issn.1001-6325.2025.01.0025

赤芍总苷减轻脑缺血/再灌注模型大鼠脑损伤

彭莹娟¹, 李志营^2*, 孙林林², 杨会杰¹, 王甜甜¹, 周丽平¹

郑州市第七人民医院 1.神经内科; 2.神经外科,河南郑州 450016

收稿日期:2024-04-28 修回日期:2024-07-24 出版日期:2025-01-05 发布日期:2024-12-25
通讯作者: ^*806451380@qq.com
基金资助:
河南省医学科技攻关计划联合共建项目(LHGJ20230741)

Total paeony glycoside alleviates brain injury of rat models developed by cerebral ischemia-reperfusion

PENG Yingjuan¹, LI Zhiying^2*, SUN Linlin², YANG Huijie¹, WANG Tiantian¹, ZHOU Liping¹

1. Department of Neurology; 2. Department of Neurosurgery, the 7th People′s Hospital of Zhengzhou, Zhengzhou 450016, China

Received:2024-04-28 Revised:2024-07-24 Online:2025-01-05 Published:2024-12-25
Contact: ^*806451380@qq.com

摘要/Abstract

摘要： 目的探究赤芍总苷(TPG)对大鼠脑缺血/再灌注损伤(CI/RI)的影响。方法将大鼠随机分为假手术组(sham组)、CI/RI模型组(单纯CI/RI组)、阳性对照药组(尼莫地平组,5 mg/kg)、低剂量TPG组(TPG-L组,27 mg/kg)、高剂量TPG组(TPG-H组,54 mg/kg)和高剂量TPG+NOD样受体热蛋白结构域相关蛋白3(NLRP3)激活剂二乙基二硫代氨基甲酸酯(DDC)组(TPG-H+DDC组,54 mg/kg TPG与30 mg/kg DDC),每组18只。给药为每日1次,连续7 d。给药结束后,进行大鼠神经功能缺损评分。尼氏染色观察大鼠脑组织神经元活性;2,3,5-氯化三苯基四氮唑(TTC)染色检测大鼠脑梗死面积;ELISA检测脑组织白细胞介素(IL)-1β、IL-18水平;Western blot检测脑组织嘌呤受体P2X配体门控性离子通道7(P2X7R)/NLRP3信号通路相关蛋白质表达与焦亡相关蛋白质如凋亡相关斑点样蛋白(ASC)、半胱氨酸天冬氨酸蛋白酶1(caspase-1)蛋白表达。结果单纯CI/RI组大鼠较假手术组大鼠神经功能缺损评分、脑梗死面积、脑组织IL-1β、IL-18水平、脑组织P2X7R、NLRP3、ASC、caspase-1蛋白表达水平显著升高(P＜0.05);脑组织尼氏小体阳性细胞比例显著降低(P＜0.05);尼莫地平组、TPG-L组、TPG-H组较单纯CI/RI组大鼠相应指标变化与上述相反(P＜0.05);NLRP3激活剂DDC减弱了TPG对CI/RI大鼠细胞焦亡的抑制作用。结论 TPG可能通过下调P2X7R/NLRP3通路抑制CI/RI大鼠脑损伤。

关键词: 赤芍总苷, P2X7R/NLRP3通路, 脑缺血/再灌注损伤, 焦亡

Abstract: Objective To investigate the effect of total paeony glycoside (TPG) on cerebral ischemia-reperfusion injury (CI/RI) of rats. Methods The rats were randomly divided into sham surgery (sham) group, CI/RI model group (simple CI/RI group), positive control group (nimodipine group, 5 mg/kg), low-dose TPG group (TPG-L group, 27 mg/kg), a high-dose TPG group (TPG-H group, 54 mg/kg)and a high-dose TPG+NOD-like receptor thermal protein domain associated protein 3 (NLRP3) activator diethyl dithiocarbamate (DDC) group (TPG-H+DDC group, 54 mg/kg TPG and 30 mg/kg DDC), with 18 rats in each, administered once a day for 7 consecutive days. After the administration, the neurological deficit score of the rats was evaluated. Nissl staining microscopy was applied to observe neuronal activity in brain tissue. 2,3,5-triphenyltetrazolium chloride (TTC) staining microscopy was applied to detect the area of cerebral infarction in rats. The level of interleukin-1β and IL-18 in brain tissue was measured by ELISA method. Western blot was applied to detect the expression of purinergic receptor P2X ligand-gated ion channel 7 (P2X7R)/NLRP3 signaling pathway related proteins and pyroptosis related proteins such as apoptosis associated speck like protein containing a CARD (ASC) and cysteine protease 1 (caspase-1) proteins in brain tissue. Results Compared with the sham group, the neurological deficit score, infarct area, level of IL-1β and IL-18 in brain tissue and protein expression of P2X7R, NLRP3, ASC, and caspase-1 in brain tissue of rats in the simple CI/RI group were significantly increased (P＜0.05), while the proportion of Nissl body positive cells in brain tissue was significantly reduced (P＜0.05). The change in corresponding indicators of rats in the nimodipine group, TPG-L group, and TPG-H group was opposite to those in the simple CI/RI group (P＜0.05). NLRP3 activator DDC antagonized the inhibitory effect of TPG on cell pyroptosis in CI/RI rats. Conclusions TPG may inhibit brain injury in CI/RI rats by down-regulating the P2X7R/NLRP3 pathway.

Key words: total paeony glycoside, P2X7R/NLRP3 pathway, cerebral ischemia-reperfusion injury, pyroptosis

中图分类号:

R743.3

彭莹娟, 李志营, 孙林林, 杨会杰, 王甜甜, 周丽平. 赤芍总苷减轻脑缺血/再灌注模型大鼠脑损伤[J]. 基础医学与临床, 2025, 45(1): 25-30.

PENG Yingjuan, LI Zhiying, SUN Linlin, YANG Huijie, WANG Tiantian, ZHOU Liping. Total paeony glycoside alleviates brain injury of rat models developed by cerebral ischemia-reperfusion[J]. Basic & Clinical Medicine, 2025, 45(1): 25-30.

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赤芍总苷减轻脑缺血/再灌注模型大鼠脑损伤

Total paeony glycoside alleviates brain injury of rat models developed by cerebral ischemia-reperfusion

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