丙泊酚通过激活Nrf2/HO-1减轻脓毒症小鼠脑损伤  

Propofol attenuates brain injury in septic mice by activating the Nrf2/HO-1 pathway

作　　者：罗涛[1] 付湘云[1] 黄蕊 刘方燕 刘永芳[1] 刘志刚[1] LUO Tao;FU Xiangyun;HUANG Rui;LIU Fangyan;LIU Yongfang;LIU Zhigang(Dept.of Anesthesiology,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei,China)

机构地区：[1]武汉大学人民医院麻醉科,湖北武汉430060

出　　处：《武汉大学学报（医学版）》2022年第5期721-726,共6页Medical Journal of Wuhan University

基　　金：湖北省自然科学基金资助项目(编号:2015CKB761)。

摘　　要：目的:探究丙泊酚对脓毒症小鼠脑损伤的影响及Nrf2/HO-1在其中的作用。方法:将60只雄性C57BL/6小鼠随机分为对照(Con)组、脓毒症(LPS)组、脂肪乳(Lip)组、丙泊酚(PF)组、丙泊酚(PF)+Nrf2抑制剂(ML385)组,每组12只。除Con组外,其他组小鼠采用腹腔注射LPS 10 mg/kg建立脓毒症小鼠脑损伤模型。注射LPS 30 min后,PF组腹腔注射50 mg/kg丙泊酚,其余各组给予等体积的药物,12 h后重复给药一次。造模成功后24 h,行神经行为评分;HE染色观察小鼠海马CA1区病理变化;ELISA法检测血清TNF-α和IL-6水平;试剂盒法检测海马组织SOD和MDA活性;Western Blot法和RT-PCR法检测脑组织中Nrf2/HO-1的mRNA和蛋白表达水平。结果:与对照组相比,脓毒症组小鼠神经功能评分降低,海马CA1区神经元损伤明显,TNF-α、IL-6和MDA水平显著升高,SOD活性显著降低,Nrf2和HO-1蛋白和mRNA表达增加(P<0.05);与脓毒症组相比,脂肪乳组上述指标的差异无统计学意义(P>0.05);丙泊酚组小鼠神经功能评分增加,海马CA1区损伤减轻,TNF-α、IL-6和MDA水平降低,SOD活性升高,Nrf2和HO-1蛋白和mRNA表达进一步增高(P<0.05);相比于丙泊酚组,Nrf2抑制剂ML385逆转了丙泊酚对脓毒症小鼠脑损伤的保护作用。结论:丙泊酚通过激活Nrf2/HO-1通路抑制炎症反应和氧化应激,进而减轻脓毒症小鼠脑损伤。Objective: To investigate the effect of propofol on brain injury in sepsis mice and the role of Nrf2/HO-1 in it. Methods: Sixty male C57BL/6 mice were randomly divided into 5 groups: Control group(Con), sepsis model(LPS), lipid treatment group(Lip), propofol treatment group(PF) and propofol+Nrf2 inhibitor group(PF+ML385). Except for the Con group, the mice in other groups were injected intraperitoneally with LPS 10 mg/kg to establish the sepsis model. 30 minutes after LPS injection, PF group mice were intraperitoneally injected with 50 mg/kg propofol, and the other groups were given the same volume of drugs. The drug was given again 12 hours later. 24 hours after sepsis models were established, the reflex test was performed to evaluate the neurological function of mice;HE staining was used to observe the pathological damage of hippocampal CA1 region in mice;the serum contents of TNF-α and IL-6 were detected by ELISA test;the activity of SOD and MDA in brain tissues were tested by assay kits;the expression of Nrf2 and HO-1 proteins were detected by RT-PCR and Western Blot. Results: Compared with Con group, the pathological damage in hippocampus CA1region, the contents of pro-inflammatory factors such as TNF-α, IL-6, and MDA were significantly increased(P<0. 05), the neurobehavioral scores and SOD levels were significantly decreased(P<0. 05), and the protein and mRNA expression levels of Nrf2 and HO-1 were increased(P<0. 05).There was no significant difference between lipid treatment group and LPS group(P>0. 05). Compared with that respectively in LPS group, the pathological damage, contents of TNF-α, IL-6, and MDA were decreased(P<0. 05), the neurobehavioral scores and SOD was markedly increased(P<0. 05), and the protein and mRNA expression levels of Nrf2 and HO-1 were significantly increased(P<0. 05) in PF group. Compared with PF group, Nrf2 inhibitor ML385 inhibited the protective effect of propofol on brain injury in septic mice. Conclusion: Propofol inhibits inflammatory responses and oxidative stress by ac

关 键 词：丙泊酚 脓毒症脑损伤 Nrf2/HO-1通路 

分 类 号：R631[医药卫生—外科学]