摘要
目的探讨厚朴酚对脓毒症小鼠血脑屏障损伤的保护作用及其分子机制。方法将60只6~8周龄雄性C57BL/6J小鼠随机分为对照组、厚朴酚(HNK)组、脂多糖(LPS)组和LPS+HNK组,每组15只。对照组腹腔注射溶剂,HNK组腹腔注射厚朴酚(10mg/kg),LPS组腹腔注射LPS(10mg/kg),LPS+HNK组腹腔注射LPS(10 mg/kg)和厚朴酚(10 mg/kg)。检测血脑屏障渗透率、大脑皮质活性氧(ROS)和丙二醛(MDA)水平,Western blot法检测紧密连接复合物(ZO-1、Claudin5、Occludin)及线粒体去乙酰化酶3(SIRT3)/超氧化物歧化酶2(SOD2)通路相关蛋白的表达。结果与LPS组比较,LPS+HNK组血脑屏障渗透率降低,ROS和MDA含量减少,紧密连接蛋白表达增加,SIRT3蛋白表达上调,乙酰化SOD2(Ac-SOD2)/SOD2比值下降(均P<0.05)。结论厚朴酚通过激活SIRT3/SOD2通路减轻大脑皮质氧化应激,从而保护脓毒症小鼠血脑屏障。
Objective To investigate whether honokiol protects against blood-brain barrier damage in septic mice and explored the underlying molecular mechanisms.Methods Male C57BL/6Jmice(6-8 weeks old,n=60)were randomly divided into four groups:control(vehicle),honokiol(HNK,10 mg/kg),lipopolysaccharide(LPS,10 mg/kg),and LPS+HNK(LPS followed by HNK)groups.Blood-brain barrier integrity was assessed using Evans blue extravasation.Cerebral microvascular endothelial cell apoptosis was evaluated by TUNEL staining.Cerebral cortex oxidative stress was measured by quantifying reactive oxygen species(ROS)and malondialdehyde(MDA)levels.Western blot analysis was performed to determine the expression of tight junction proteins(ZO-1,Claudin-5,Occludin)and SIRT3/SOD2 pathway components.Results LPS+HNK treatment significantly reduced Evans blue extravasation and endothelial cell apoptosis compared to LPS alone.The treatment also decreased ROS and MDA levels(both P<0.05),enhanced tight junction protein expression,increased SIRT3 level,and reduced Ac-SOD2/SOD2 ratio(all P<0.05).ConclusionHonokiol can protect the blood-brain barrier in septic mice by activating the SIRT3/SOD2 pathway and reduce oxidative stress in the cerebral cortex.
作者
高秀钗
林洁
钱彬
GAO Xiuchai;LIN Jie;QIAN Bin(Department of Anesthesiology,Fujian Xiapu County Hospital,Xiapu,Fujian 355199,China;Department of Anesthesiology,People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine,Fuzhou,Fujian 350004,China)
出处
《福建医药杂志》
2025年第6期68-72,共5页
Fujian Medical Journal
基金
宁德市自然科学基金项目(2022J58)
福建省卫生健康科技计划项目(2024CXA046)。
