湖北中医药大学学报2024,Vol.26Issue(1) :17-21.DOI:10.3969/j.issn.1008-987x.2024.01.03

知母皂苷B-Ⅱ通过激活cAMP/PKA/CREB途径减轻大鼠脑缺血再灌注诱导的损伤

Zhimu saponin B-Ⅱ reduces cerebral ischemia-reperfusion induced injury in rats by activating the cAMP/PKA/CREB pathway

刘洁 胡毅 丁玲 贺小艳 夏春勇 曹烈臻 李小亚 范颖 张作文
湖北中医药大学学报2024,Vol.26Issue(1) :17-21.DOI:10.3969/j.issn.1008-987x.2024.01.03

知母皂苷B-Ⅱ通过激活cAMP/PKA/CREB途径减轻大鼠脑缺血再灌注诱导的损伤

Zhimu saponin B-Ⅱ reduces cerebral ischemia-reperfusion induced injury in rats by activating the cAMP/PKA/CREB pathway

刘洁 1胡毅 1丁玲 1贺小艳 1夏春勇 1曹烈臻 1李小亚 1范颖 1张作文1
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作者信息

  • 1. 重庆大学附属江津医院,重庆 402260;重庆市江津区中心医院,重庆 402260
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摘要

目的 观察知母皂苷B-Ⅱ(TB-Ⅱ)通过抑制cAMP/PKA/CREB途径减轻对脑缺血再灌注大鼠损伤(CIRI)的疗效.方法 将大鼠随机分为6组:假手术组,模型组,TB-Ⅱ低、中、高剂量组,尼莫地平组.采用"Longa"线栓法建立大鼠大脑中动脉闭塞模型后,检测各组大鼠神经功能评分,脑梗死面积、脑含水量、脑埃文斯蓝(EB)含量测定;通过免疫荧光染色观察大脑神经元结构损伤及神经元凋亡情况;通过ELISA检测和Western Blot检测炎症因子及相关通路蛋白水平表达.结果 与假手术组比较,模型组EB含量增加(P<0.05);与模型组比较,尼莫地平组脑含水量、EB含量、脑梗死面积等均降低(P<0.05,P<0.01),中、高剂量组脑含水量降低(P<0.05),各剂量组EB含量、脑梗死面积均降低(P<0.05,P<0.01);TB-Ⅱ各组均不同程度地下调IL-1β、IL-6和TNF-α等炎症因子的分泌(P<0.05),并通过PKA/CREB通路,降低AQP-4蛋白的表达(P<0.05).结论 本研究揭示了 TB-Ⅱ通过cAMP/PKA/CREB通路,减轻大鼠脑缺血再灌注损伤的作用机制.

Abstract

Objective To observe the therapeutic effect of Zhimu saponinB-11(TB-Ⅱ)on cerebral ischemia-reperfusion injury(CIRI)by inhibiting the cAMP/PKA/CREB pathway.Methods Rats were randomly divided into 6 groups:sham surgery group,model group,low-dose TB-Ⅱ group(10 mg/kg),medium dose TB-Ⅱ group(20 mg/kg),high-dose TB-Ⅱ group(40 mg/kg),and nimodipine treatment group(12 mg/kg).After establishing a rat model of middle cerebral artery occlusion using the Longa suture method,the neurological function scores,infarct area,brain water content,and Evans blue(EB)content of each group of rats were measured;observe the structural damage and neuronal apoptosis of brain neurons through Nissl staining and immunofluorescence staining;the expression levels of inflammatory factors and related pathway proteins were detected by ELISA and Western Blot.Results Compared with sham surgery group,the EB content in model group increased(P<0.05);compared with model group,the brain water content,EB content,and cerebral infarction area of nimodipine group decreased(P<0.05,P<0.01),while the brain water content of the medium and high dose groups decreased(P<0.05);the EB content and cerebral infarction area of each dose group decreased(P<0.05,P<0.0 1);meanwhile,all dose groups of TB-Ⅱ were able to downregulate interluekin-1(IL-1)to varying degrees IL-1β,IL-6 and tumor necrosis factor-α(TNF-α);the secretion of inflammatory factors was regulated(P<0.05),and the expression of AQP-4 protein was reduced through the PKA/CREB pathway(P<0.05).Conclusion This study revealed that TB-Ⅱ alleviates cerebral ischemia-reperfusion injury in rats through the PKA/CREB pathway.

关键词

脑缺血再灌注/知母皂苷B-Ⅱ/尼莫地平

Key words

Cerebral ischemia-reperfusion/Zhimu saponin B-Ⅱ/Nimodipine

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基金项目

重庆市自然科学基金(cstc2020jcyjmsxmX0434cstc2021jcyjmsxmX0724)

重庆市临床药学重点专科学科经费资助项目(2022-07)

出版年

2024
湖北中医药大学学报
湖北中医药大学

湖北中医药大学学报

CSTPCD
影响因子:0.873
ISSN:1008-987X
参考文献量15
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