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。
Objective To observe the therapeutic effect of Zhimu saponin B-Ⅱ(TB-Ⅱ)on cerebral ischemia-reperfusion injury(CIRI)by inhibiting the c AMP/PKA/CREB pathway.Methods Rats were randomly divided into 6 groups:sham surgery group,model group,low-dose TB-Ⅱgroup(10 mg/kg),medium dose TB-Ⅱgroup(20 mg/kg),high-dose TB-Ⅱgroup(40mg/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<0.01);meanwhile,all dose groups of TB-Ⅱwere 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-Ⅱalleviates cerebral ischemia-reperfusion injury in rats through the PKA/CREB pathway.
作者
刘洁
胡毅
丁玲
贺小艳
夏春勇
曹烈臻
李小亚
范颖
张作文
LIU Jie;HU Yi;DING Ling;HE Xiao-yan;XIA Chun-yong;CAO Lie-zhen;LI Xiao-ya;FAN Ying;ZHANG Zuo-wen(Chongqing University Jiangjin Hospital Affiliated to,Chongqing 402260;Jiangjin District Central Hospital of Chongqing,Chongqing 402260)
出处
《湖北中医药大学学报》
2024年第1期17-21,共5页
Journal of Hubei University of Chinese Medicine
基金
重庆市自然科学基金项目(项目编号:cstc2020jcyj-msxmX0434,cstc2021jcyj-msxmX0724)
重庆市临床药学重点专科学科经费资助项目(项目编号:2022-07)。
