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    王玉, 彭思亮, 朱江, 陶苏蔚, 武玉清. 胍丁胺对大鼠术后中枢炎症反应和认知功能障碍的影响[J]. 徐州医科大学学报, 2022, 42(5): 336-342. DOI: 10.3969/j.issn.2096-3882.2022.05.005
    引用本文: 王玉, 彭思亮, 朱江, 陶苏蔚, 武玉清. 胍丁胺对大鼠术后中枢炎症反应和认知功能障碍的影响[J]. 徐州医科大学学报, 2022, 42(5): 336-342. DOI: 10.3969/j.issn.2096-3882.2022.05.005
    Agmatine attenuates postoperative cognitive dysfunction by reducing neuroinflammation[J]. Journal of Xuzhou Medical University, 2022, 42(5): 336-342. DOI: 10.3969/j.issn.2096-3882.2022.05.005
    Citation: Agmatine attenuates postoperative cognitive dysfunction by reducing neuroinflammation[J]. Journal of Xuzhou Medical University, 2022, 42(5): 336-342. DOI: 10.3969/j.issn.2096-3882.2022.05.005

    胍丁胺对大鼠术后中枢炎症反应和认知功能障碍的影响

    Agmatine attenuates postoperative cognitive dysfunction by reducing neuroinflammation

    • 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。

       

      Abstract: ob<x>jective:This study aimed to observe the effects of agmatine on neuroinflammation and cognitive function after anesthesia and surgery in adult rats.Methods:Sprague-Dawley rats were randomly divided into five groups, NS group, NS+anesthesia and surgery group(NS+Sur),low-dose,medium-dose and high-dose agmatine+anesthesia and surgery group (AGM20mg/kg+Sur,AGM40mg/kg+Sur,AGM80mg/kg+Sur).Each group underwent splenectomy with sevoflurane anesthesia, and learning and memory abilities were tested by Morris water maze.The ex<x>pression of TNF-α, IL-1β and IL-6 in the hippocampus were detected by ELISA on postoperative day 3.We used western blot to detect the ex<x>pression of the ex<x>pression of p-NF-κB p65 in the hippocampus and the ZO-1 and Occ in the brain microvascular. The ex<x>pression of GFAP in hippocampal astrocytes was detected by immunofluorescence.The permeability of blood-brain barrier in rats was detected by Evans blue.Results:Three days after anesthesia, the cognitive function of NS+Sur group was significantly decreased compared with that of NS group (P<0.01). The ex<x>pression levels of p-NF -κB P65, IL-1β, IL-6, TNF-α and GFAP in the hippocampus of NS+Sur group were significantly increased, the ex<x>pression levels of ZO-1 and Occ in brain microvessels were significantly decreased, and the exudation of Evans blue in brain tissue was significantly increased (P<0.01). Compared with NS+Sur group, the cognitive function of AGM80+Sur group was improved (P<0.05, P<0.01); the ex<x>pression levels of p-NF -κB P65, IL-1β, IL-6, TNF-α and GFAP in hippocampus of AGM80+Sur group were significantly decreased, the ex<x>pression levels of ZO-1 and Occ in brain microvessels were significantly increased, and the exudation of Evans blue in brain tissue was significantly decreased (P<0.01).Conclusions:Agmatine can reduce central nervous system inflammation, blood-brain barrier permeability and cognitive dysfunction after anesthesia and surgery in SD rats.

       

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