[1]许雯,郭予斌,李旭,等.棕榈酸通过肝细胞氧化应激反应激活炎症小体[J].南方医科大学学报,2016,(05):655.
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棕榈酸通过肝细胞氧化应激反应激活炎症小体()
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《南方医科大学学报》[ISSN:/CN:]

卷:
期数:
2016年05期
页码:
655
栏目:
出版日期:
2016-05-15

文章信息/Info

Title:
Palmitic acid induces hepatocellular oxidative stress and activation of inflammasomes
作者:
许雯郭予斌李旭何美蓉刘思德
关键词:
棕榈酸NADPH氧化酶4线粒体氧化应激炎症小体
Keywords:
palmitic acid NADPH oxidase 4 mitochondria oxidative stress inflammasomes
摘要:
目的观察棕榈酸(PA)对肝细胞氧化应激反应及炎症小体产生的影响。方法(1)将正常小鼠肝细胞AML12分别用不同 浓度的棕榈酸(0、0.15、0.25、0.4 mmol/L)处理;(2)将AML12细胞分为空白对照组(control组)、棕榈酸组(PA组)及棕榈酸+N-乙 酰半胱氨酸组(PA+NAC组)并予以相应药物处理。24 h后检测细胞中脂肪沉积情况、细胞总ROS、线粒体来源ROS、NOX4蛋 白表达、NOX4的定位以及炎症小体和IL-1β的表达。结果与control组相比,PA组细胞质中脂滴增加,细胞总ROS(12463.09± 2.72 vs 6691.23±2.45,P=0.00)及线粒体来源ROS含量(64.98±0.94 vs 45.04±0.92,P=0.00)上升,NOX4、NLRP3、ASC、caspase-1 蛋白表达增加,IL-1β表达增加(1603.52±1.32 vs 2629.33±2.57,P=0.00),且发现线粒体和NOX4在细胞质中存在共定位,而抗氧 化剂NAC除了能使PA诱导的ROS产生减少(7782.15±2.87 vs 5445.6±1.17,P=0.00),还可使NLRP3、ASC及caspase-1蛋白表 达下降。结论棕榈酸刺激肝细胞后,可以导致脂滴在肝细胞质中大量沉积,亦可以通过线粒体和NOX4途径导致肝细胞氧化 应激反应,并因此促进细胞炎症小体的激活和IL-1β的分泌。
Abstract:
Objective To evaluate the effect of palmitic acid (PA) on oxidative stress and activation of inflammasomes in hepatocytes. Methods To test the dose-dependent effect of PA on normal murine hepatocytes AML12, the cells were treated with 0, 0.15, 0.25 and 0.4 mmol/L of palmitic acid (PA). The cells were also divided into blank control group, 0.25 mmol/L PA group and 0.25 mmol/L PA+ N-acetylcysteine (NAC) group to examine the effect of reactive oxygen species (ROS) on the activation of inflammasomes. After 24 h of treatment, lipid accumulation, total ROS, mitochondrial ROS, expression and localization of NOX4, and expressions of inflammasomes and IL-1β were detected in the hepatocytes. Results Compared with the control cells, PA treatment of the cells significantly increased cytoplasmic lipid accumulation, concentrations of total ROS (12 463.09 ± 2.72 vs 6691.23 ± 2.45, P=0.00) and mitochondrial ROS (64.98 ± 0.94 vs 45.04 ± 0.92, P=0.00), and the expressions of NOX4, NLRP3, ASC, caspase-1, and IL-1β (1603.52±1.32 vs 2629.33±2.57, P=0.00). The mitochondria and NOX4 were found to be co-localized in the cytoplasm. NAC obviously reduced cellular ROS level stimulated by PA (7782.15±2.87 vs 5445.6±1.17, P= 0.00) and suppressed the expressions of NLRP3, ASC and caspase-1. Conclusion PA treatment can stimulate lipid accumulation in hepatocytes and induce oxidative stress through NOX4 and mitochondria pathway to activate inflammasomes and stimulate the secretion of IL-1β.
更新日期/Last Update: 1900-01-01