七氟醚在脓毒症大鼠模型中通过半胱天冬蛋白酶3/9和Bax/Bcl信号通路对抗脓毒症相关脑病和记忆障碍而发挥脑保护作用
祝贺贵州医科大学麻醉学院15级科学学位研究生易菁顺利毕业
研究方向:麻醉与心脏电生理 指导老师:高鸿教授 段宏伟 曾庆繁
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Sevoflurane exerts brain-protective effects against sepsis-associated encephalopathy and memory impairment through caspase 3/9 and Bax/Bcl signaling pathway in a rat model of sepsis
背景与目的
本研究通过盲肠结扎穿孔术（CLP）诱导多细菌性腹膜炎从而制成脓毒症相关脑病大鼠模型，比较七氟醚和异氟醚对系统性炎症、脓毒症相关脑病的影响。
方 法
将24只大鼠随机分为四组：假手术组、CLP组、CLP+七氟醚组和CLP+异氟醚组。在CLP 72小时后，对大鼠进行行为学测试，并对其血清细胞因子进行测定评估。收集脑组织标本，测定谷胱甘肽过氧化物酶（GPX)、超氧化物歧化酶（SOD)、过氧化氢酶；湿/干重比；髓过氧化物酶（MPO)和丙二醛（MDA)；凋亡基因表达；组织学检测。
结 果
与CLP组相比，CLP+七氟醚组和CLP+异氟醚组的MPO水平、湿/干重比、组织病理学评分均较低，并且Bcl2a-l和Bcl21-2表达均上调。与CLP+异氟醚组相比，CLP+七氟醚组的白介素-6、白介素-lβ、MDA以及半胱天冬蛋白酶3、8、9水平较低；GPX、SOD、Bax、Bcl2、Bclx表达水平较高.
结 论
在CLP大鼠模型中，七氟醚可降低大鼠细胞凋亡和氧化损伤，改善大鼠记忆能力。七氟醚镇静对于脓毒症患者可能具有对抗脑损伤和记忆障碍的保护性作用。
原始文献摘要
Nurdan Bedirli, Emin Umit Bagriacik,Guldal Yilmaz；Sevoflurane exerts brain-protective effects against sepsis-associated encephalopathy and memory impairment through caspase 3/9 and Bax/Bcl signaling pathway in a rat model of sepsis；Journal of International Medical Research0(0) 1–15 ,The Author(s) 2018Reprints and permissions:sagepub.co.uk/journalsPermissions.navDOI: 10.1177/0300060518773265。
Abstract:
Objective: We compared the effects of sevoflurane and isoflurane on systemic inflammation,sepsis-associated encephalopathy, and memory impairment in a rat sepsis model of cecal ligation and puncture (CLP)-induced polymicrobial peritonitis.
Methods: Twenty-four rats were assigned to sham, CLP, CLPtsevoflurane, and CLPtisoflurane groups. At 72 hours after CLP, the rats underwent behavior tests. Serum cytokines were evaluated. Brain tissue samples were collected for determination of glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase; the wet/dry weight ratio; myeloperoxidase (MPO) and malondialdehyde (MDA); apoptotic gene release; and histologic examinations.
Results: The MPO level, wet/dry weight ratio, and histopathology scores were lower and the Bcl2a1 and Bcl2l2 expressions were upregulated in both the CLPtsevoflurane and CLP tisoflurane groups compared with the CLP group. The interleukin-6, interleukin-1b, MDA, and caspase 3, 8, and 9 levels were lower; the GPX, SOD, Bax, Bcl2, and Bclx levels were higher; and non-associative and aversive memory were improved in the CLPtsevoflurane group compared with the CLPtisoflurane group.
Conclusion: Sevoflurane decreased apoptosis and oxidative injury and improved memory in this experimental rat model of CLP. Sevoflurane sedation may protect against brain injury and memory impairment in septic patients.
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