菊苣酸对脓毒症大鼠心肌损伤时氧化应激的影响及其与Nrf2信号通路的关系

被引:9
作者
李依玲 [1 ]
姚鹏 [2 ]
祁皓 [2 ]
卢忆萍 [1 ]
毛毅 [1 ]
孟杰 [1 ]
肖航
机构
[1] 武汉科技大学附属孝感医院麻醉科
[2] 武汉科技大学附属孝感医院重症医学科
关键词
咖啡酸类; 脓毒症; 心脏损伤; 氧化性应激; NF-E2相关因子2;
D O I
暂无
中图分类号
R285.5 [中药实验药理];
学科分类号
100806 [中药药理学];
摘要
目的评价菊苣酸对脓毒症大鼠心肌损伤时氧化应激的影响及其与核因子E2相关因子2(Nrf2)信号通路的关系。方法健康雄性SD大鼠40只, 8~12周龄, 体重220~250 g, 采用随机数字表法分为5组(n=8):对照组(C组)、LPS组、LPS+菊苣酸组(LPS+CA组)、LPS+Nrf2抑制剂ML385组(LPS+ML组)和LPS+菊苣酸+ML385组(LPS+CA+ML组)。腹腔注射LPS 15 mg/kg制备大鼠脓毒症心肌损伤模型。腹腔注射LPS即刻, LPS+CA组和LPS+ML组分别腹腔注射菊苣酸10 mg/kg或ML385 15 mg/kg(均用DMSO溶解), LPS+CA+ML组腹腔注射ML385 15 mg/kg和菊苣酸10 mg/kg, C组腹腔注射等容量DMSO。造模后48 h时, 取主动脉血样, 采用ELISA法测定血清IL-6浓度、LDH和CK-MB活性。然后处死大鼠, 取心肌组织, HE染色后光镜下观察病理学结果, 采用化学比色法测定谷胱甘肽过氧化物酶(GSH-Px)和SOD活性、ROS和铁含量, 计算NAD+/NADH比值, 采用Western blot法测定Nrf2、醌氧化还原酶1(NOQ1)、谷胱甘肽过氧化物酶4(GPX4)和尼克酰胺腺嘌呤二核苷酸磷酸氧化酶1(NOX1)的表达水平。结果与C组相比, 其余4组血清LDH、CK-MB活性和IL-6浓度升高, 心肌组织ROS和铁含量及NAD+/NADH比值升高, GSH-Px和SOD活性降低, Nrf2、NQO1和GPX4表达下调, NOX1表达上调(P<0.05);与LPS组相比, LPS+CA组血清LDH、CK-MB含量和IL-6浓度降低, 心肌组织ROS和铁含量及NAD+/NADH比值降低, GSH-Px和SOD活性升高, Nrf2、NQO1和GPX4表达上调, NOX1表达下调(P<0.05), 心肌细胞病理学损伤明显减轻, LPS+ML组血清LDH、CK-MB含量和IL-6浓度升高, 心肌组织NAD+/NADH比值升高, GSH-Px和SOD活性降低, NQO1和GPX4表达下调, NOX1表达上调(P<0.05), 心肌细胞病理学损伤进一步加重;与LPS+CA组相比, LPS+CA+ML组血清LDH、CK-MB活性和IL-6浓度升高, 心肌组织ROS和铁含量及NAD+/NADH比值升高, GSH-Px和SOD活性降低, Nrf2、GPX4和NQO1表达下调, NOX1表达上调(P<0.05), 心肌细胞病理学损伤明显加重。结论菊苣酸减轻脓毒症大鼠心肌损伤的机制可能与激活Nrf2信号通路, 抑制氧化应激有关。
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