摘要
目的观察胍丁胺对成年SD大鼠术后中枢神经炎症和认知功能的影响。方法将SD大鼠随机分为5组,生理盐水组(NS)、生理盐水+麻醉手术组(NS+Sur)及低、中、高剂量胍丁胺(20、40、80 mg/kg)+麻醉手术组(AGM20+Sur、AGM40+Sur、AGM80+Sur)。各组大鼠在七氟醚麻醉下行脾脏切除手术,通过Morris水迷宫测试学习记忆能力。在麻醉手术后3 d,采用ELISA法检测海马肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的表达情况;Western blot技术检测海马磷酸化核因子-κB p65(p-NF-κB p65)以及紧密连接蛋白-1(ZO-1)、闭锁蛋白(Occ)的表达情况;通过免疫荧光技术检测海马胶质纤维酸性蛋白(GFAP)的表达水平;应用依文思蓝(EB)法检测大鼠血脑屏障通透性。结果麻醉手术后3 d,与NS组相比,NS+Sur组大鼠的认知功能明显下降(P<0.01),海马组织p-NF-κB p65、IL-1β、IL-6、TNF-α以及GFAP的表达水平均显著升高,脑微血管ZO-1和Occ的表达均显著减少,脑组织渗出的EB则显著增多(P<0.01)。与NS+Sur组相比,AGM80+Sur组大鼠的认知功能提高(P<0.05),海马组织p-NF-κB p65、IL-1β、IL-6、TNF-α以及GFAP的表达水平均显著降低,脑微血管ZO-1和Occ的表达均显著增强,脑组织渗出的依文思蓝显著减少(P<0.01)。结论胍丁胺能够减轻SD大鼠术后中枢炎症反应,降低血脑屏障的通透性,改善术后认知功能障碍。
Objective To observe the effects of agmatine on neuroinflammation and cognitive function in adult rats after surgery.Methods SD rats were randomly divided into five groups:a normal saline(NS)group,a NS+surgery under anesthesia(NS+Sur)group,and low-,medium-and high-dose agmatine+surgery under anesthesia(AGM 20 mg/kg+Sur,AGM 40 mg/kg+Sur,and AGM 80 mg/kg+Sur)groups.Each group underwent splenectomy with sevoflurane anesthesia.Their learning and memory abilities were tested by Morris maze.Then,three days after surgery,the levels of tumor necrosis factor(TNF)-α,interleukin(IL)-1βand IL-6 in the hippocampus were detected by ELISA.The amounts of p-nuclear factor(p-NF)-κB p65 in the hippocampus,and ZO-1 and Occ were detected by Western blot.The expression of GFAP in hippocampal astrocytes was detected by immunofluorescence.The permeability of the blood-brain barrier in rats was detected by Evans blue.Results Three days after anesthesia,compared with the NS group,the NS+Sur group showed significantly decreased cognitive function(P<0.01),increased levels of p-NF-κB P65,IL-1β,IL-6,TNF-αand GFAP in the hippocampus,significantly decreased expression of ZO-1 and Occ in brain microvessels,and significantly increased exudation of Evans blue in brain tissue(P<0.01).Compared with the NS+Sur group,the AGM80+Sur group showed significantly enhanced cognitive function(P<0.05),reduced levels of p-NF-κB P65,IL-1β,IL-6,TNF-αand GFAP in the hippocampus,significantly increased expression of ZO-1 and Occ in brain microvessels,and significantly depresssed exudation of Evans blue in brain tissue(P<0.01).Conclusions Agmatine can reduce neural inflammation,decrease blood-brain barrier permeability and improve cognitive dysfunction.
作者
王玉
彭思亮
朱江
陶苏蔚
武玉清
WANG Yu;PENG Siliang;ZHU Jiang;TAO Suwei;WU Yuqing(Department of Anesthesiology,the Second Hospital Affiliated to Suzhou University,Suzhou,Jiangsu 215004,China;Department of Cardiology,the Second Hospital Affiliated to Suzhou University;Jiangsu Province Key Laboratory of Anesthesiology,Xuzhou Medical University,Xuzhou,Jiangsu 221004)
出处
《徐州医科大学学报》
CAS
2022年第5期336-342,共7页
Journal of Xuzhou Medical University
基金
苏州市民生科技医疗卫生应用基础研究(SYS2019074)
苏州市民生科技关键技术应用研究(SKY2021042)。
关键词
胍丁胺
麻醉手术
神经炎症
血脑屏障
术后认知功能障碍
agmatine
surgery under anesthesia
neuroinflammation
blood brain barrier
postoperative cognitive impairment
