摘要
目的探究利多卡因对脓毒症相关性脑病模型大鼠的脑保护作用及机制。方法将40只大鼠按随机数字表法分为对照组、模型组、利多卡因组、利多卡因+血管紧张素受体AT1相关的受体蛋白拮抗剂Apelin13(F13A)组,每组10只。除对照组外,其余3组大鼠均构建脓毒症相关性脑病模型,利多卡因组和利多卡因+F13A组造模后即刻给予利多卡因10 mg/kg负荷剂量,随后尾iv利多卡因10 mg/kg并持续3 h,利多卡因+F13A组同时ip APJ拮抗剂F13A 100μg/kg。24 h后,Morris水迷宫实验检测各组大鼠认知功能,酶联免疫吸附(ELISA)法检测各组大鼠血清白细胞介素(IL)-6、IL-10、肿瘤坏死因子-α(TNF-α)水平,苏木精–伊红(HE)染色观察各组大鼠脑组织病理变化,TdT介导的dUTP缺口末端标记法(TUNEL)和神经元特异核蛋白(NeuN)双免疫荧光染色检测各组大鼠脑组织皮质内神经元凋亡,免疫荧光双染法观察各组大鼠脑组织皮质内Apelin与APJ表达,实时荧光定量逆转录聚合酶链反应(RT-qRCR)检测各组大鼠脑组织Apelin和APJ的mRNA表达,蛋白质免疫印迹(Western blotting)法检测各组大鼠脑组织Apelin和APJ的蛋白表达。结果与模型组比较,利多卡因组大鼠逃避潜伏期缩短,通过目标象限次数增加(P<0.05),血清IL-6、TNF-α水平降低而IL-10水平显著升高(P<0.05),海马区神经元损伤明显减轻,形态和分布均趋于正常,脑组织皮质内凋亡神经元数目减少(P<0.05);Apelin与APJ荧光染色表达均明显增强,脑组织内Apelin、APJ的mRNA与蛋白相对表达量均显著上调(P<0.05);与利多卡因组比较,利多卡因+F13A组大鼠逃避潜伏期延长,通过目标象限次数减少(P<0.05),血清IL-6、TNF-α水平升高,血清IL-10水平显著降低(P<0.05),海马区神经元损伤加重,有大量细胞肿胀与细胞核固缩,脑组织皮质内凋亡神经元数目增加(P<0.05)。同时,Apelin与APJ荧光染色表达均明显减弱,脑组织内Apelin、APJ的mRNA与蛋�
Objective To investigate the protective effects and mechanism of lidocaine on sepsis-associated encephalopathy model rats.Methods Forty rats were randomly divided into control group,model group,lidocaine group,and lidocaine+F13A group,with 10 rats in each group.Except the control group,the other three groups of rats were constructed sepsis-associated encephalopathy model,lidocaine group and lidocaine+F13A group were given a loading dose of 10 mg/kg lidocaine immediately after modeling,after that,lidocaine 10 mg/kg was injected intravenously for 3 h,APJ antagonist F13A 100μg/kg was injected intraperitoneally in lidocaine+F13A group.24 h later,the Morris water maze test detected the cognitive function of each group,enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of serum interleukin(IL)-6,IL-10,and tumor necrosis factor-α(TNF-α),hematoxylin-eosin(HE)staining was used to observe pathological changes in brain tissue of rats in each groups,TdT mediated dUTP nick end labeling(TUNEL)and neuron-specific nuclear protein(NeuN)double immunofluorescence staining was used to detect neuronal apoptosis in the cerebral cortex of each group,the expressions of Apelin and APJ in the cerebral cortex of rats in each group were observed by immunofluorescence double staining,real-time polymerase chain reaction(RT-qRCR)was used to detect the mRNA expressions of Apelin and APJ in the brain tissues of rats in each group,Western blotting was used to detect the protein expressions of Apelin and APJ in the brain tissues of rats in each group.Results Compared with model group,the escape latency of rats in lidocaine group was shortened,the number of target quadrant was increased(P<0.05),the levels of IL-6 and TNF-αin serum were decreased while the level of IL-10 was increased(P<0.05),the damage of neurons in hippocampus was significantly reduced,and the morphology and distribution of neurons tended to be normal,the number of apoptotic neurons in the cerebral cortex was decreased(P<0.05),the expression of Apelin and AP
作者
张雯
张宇轩
李瑞轩
徐桂萍
ZHANG Wen;ZHANG Yu-xuan;LI Rui-xuan;XU Gui-ping(People's Hospital of Xinjiang Uygur Autonomous Region,Xinjiang Clinical Research Center for Anesthesia Management,Urumqi 830000,China)
出处
《现代药物与临床》
CAS
2023年第2期249-256,共8页
Drugs & Clinic
基金
新疆维吾尔自治区卫生健康青年医学科技人才专项科研项目(WJWY-202203)。
