当归逐瘀胶囊对CI/RI大鼠大脑皮层组织NF-κB介导的炎症反应的影响  

Effect of Danggui Zhuyu Capsule on NF-κB Mediated Inflammatory Response in Cerebral Cortex Tissue of CI/RI Rats

作　　者：池宁娟 刘明义 徐芳琴 石小鹏 杨志福 赵超 赵涛 王靖雯 CHI Ningjuan;LIU Mingyi;XU Fangqin;SHI Xiaopeng;YANG Zhifu;ZHAO Chao;ZHAO Tao;WANG Jingwen(First Affiliated Hospital of Air Force Medical University,Xi'an 710032,China)

机构地区：[1]空军军医大学第一附属医院,陕西西安710032

出　　处：《陕西中医药大学学报》2024年第3期99-104,共6页Journal of Shaanxi University of Chinese Medicine

基　　金：国家自然科学基金面上项目(81573549)。

摘　　要：目的探讨当归逐瘀胶囊对大鼠脑缺血再灌注损伤(cerebral ischemia reperfusion injury,CI/RI)不同时间点大脑损伤侧皮层组织中核因子-κB(NF-κB)信号通路及炎症反应的影响。方法取健康雄性大鼠120只,随机分成假手术组、模型组和当归逐瘀组,每组按照缺血后再灌注24 h、48 h、72 h和10 d各分为4个亚组。除假手术组外,剩余各组采用线栓法制备大鼠MCAO模型,缺血2 h,待大鼠清醒回笼后灌胃给药。假手术组和模型组灌胃给予生理盐水10 mL·kg^(-1),当归逐瘀组灌胃给予药物2.00 g·kg^(-1),每天1次。取脑组织TTC染色法测定梗死面积,HE染色观察组织病理学变化,RT-PCR测定TNF-α、IL-8、ICAM-1和MCP-1 mRNA表达,Western blotting检测IKKβ和NF-κB65蛋白表达。结果当归逐瘀胶囊能显著降低再灌注各时间点脑梗死面积(P<0.05);有效改善大脑皮层组织病理损伤;显著降低再灌注24 h~10 d TNF-αmRNA、ICAM-1mRNA、MCP-1 mRNA和p-NF-κB65蛋白表达,降低再灌注24 h~48 h IL-8 mRNA和IKKβ蛋白表达(P<0.05)。结论当归逐瘀胶囊有脑保护作用,其作用机制可能是通过调控IKKβ和p-NF-κB65蛋白、降低TNF-α、IL-8、ICAM-1和MCP-1 mRNA表达、抑制炎症反应而发挥脑保护作用。Objective To explore the effects of Danggui Zhuyu capsules on the nuclear factorκB(NF-κB)signaling pathway and inflammatory response in the cortical tissue of the injured side of the brain at different time points of cerebral ischemia-reperfusion injury(CI/RI)in rats.Methods 120 rats were randomly divided into a sham surgery group,a model group,and an Angelica sinensis stasis removing group.Each group was further divided into four subgroups based on reperfusion for 24 hours,48 hours,72 hours,and 10 days,respectively.Except for the sham surgery group,the other groups prepared rat MCAO models using thread occlusion method.After 2 hours of ischemia,the rats were given gastric lavage after waking up.The sham surgery group and model group were given distilled water of 10 mL·kg^(-1) by gastric lavage,while the Danggui Zhuyu group was given gastric lavage 2.00 g·kg^(-1),once a day.Brain tissue was taken for TTC staining to determine infarct area,HE staining to observe histopathological changes,and RT-PCR to determine TNF-α、IL-8、ICAM-1and MCP-1 mRNA expression,Western blotting for IKKβand NF-κB65 protein expression.Results The results showed that Danggui Zhuyu capsules could significantly reduce the area of cerebral infarction at various time points of reperfusion(P<0.05);Effectively improving pathological damage to cerebral cortex tissue;Significantly reduce TNF after reperfusion for 24 hours to 10 days-αMRNA,ICAM-1 mRNA,MCP-1 mRNA,and p-NF-B65 protein expression were reduced,while IL-8 mRNA and IKK protein expression were reduced from 24 hours to 48 hours after reperfusion(P<005).Conclusion Danggui Zhuyu Capsule has a neuroprotective effect,and its mechanism of action may be through regulating IKKβand p-NF-κB65 proteins,and reducing TNF-αmRNA、ICAM-1mRNA、MCP-1 mRNA and p-NF-κB65 mRNA expression,exert neuroprotective effects by inhibiting inflammatory responses.

关 键 词：当归逐瘀胶囊 脑缺血再灌注损伤 炎症反应 核因子-κB 

分 类 号：R285.5[医药卫生—中药学]