曲美他嗪对急性肝衰竭小鼠肝组织NOX2和NOX4表达的影响

doi:10.3969/j.issn.1672-5069.2021.06.008

摘要/Abstract

摘要： 目的探讨曲美他嗪对急性肝衰竭小鼠肝组织NOX2和NOX4表达的影响。方法随机将65只C57BL/6小鼠分为对照组、模型组、小、中、大剂量曲美他嗪处理组和还原型谷胱甘肽处理组,除模型组15只外,其他组均为10只。采用D-氨基半乳糖联合脂多糖腹腔注射建立急性肝衰竭模型。取肝组织匀浆检测丙二醛(MDA)和过氧化物酶(CAT)含量,采用RT-PCR法和Western blot法分别检测肝组织还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶( NOX2/4) mRNA水平和蛋白表达。结果模型组血清ALT、AST和肝匀浆MDA水平分别为(121.4±3.7)U/L、(208.9±27.4)U/L和(51.0±20.5)nmol/mg,均显著高于对照组【分别为(35.3±3.2)U/L、(49.9±4.4)U/L和(14.1±5.2)nmol/mg,P＜0.05】,而模型组肝匀浆CAT水平为(51.7±16.8)U/mg,显著低于对照组【(110.2±33.7)U/mg,P＜0.05】;模型组NOX2/4 mRNA和蛋白相对水平分别为(8.2±2.0)/(1.2±0.1)和(2.6±0.1)/(1.3±0.1),均显著高于对照组【分别为(1.0±0.2)/(0.5±0.1)和(1.0±0.1)/(0.4±0.1),P＜0.05】,中、大剂量曲美他嗪处理组血清ALT和AST及肝匀浆MDA水平分别为(86.4±1.00)U/L、(154.0±6.2)U/L和(22.5±1.9)nmol/mg及(81.1±1.5)U/L、(134.7±5.3)U/L和(20.1±3.7)nmol/mg,均显著低于模型组【分别为(121.4±3.7)U/L、(208.9±27.4)U/L和(51.0±20.5)nmol/mg,P＜0.05】,肝匀浆CAT水平分别为(99.4±15.5)和(102.3±15.5),均显著高于模型组【(51.6±16.8),P＜0.05】;肝组织NOX2/4 mRNA及蛋白相对表达量分别为(5.6±0.2)/(0.7±0.0)和(5.2±1.4/0.6±0.1)及(1.7±0.2)/(0.7±0.2)和(1.5±0.1)/(0.6±0.2),均显著低于模型组【(8.2±2.0)/(1.2±0.1)和(2.6±0.1)/(1.3±0.1),P＜0.05】。结论曲美他嗪可能通过下调肝组织NOX2/4表达减轻氧化应激损伤,改善D-Galn/LPS诱导的急性肝衰竭小鼠肝损伤。

关键词: 急性肝衰竭, 曲美他嗪, 氧化应激, 还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶2/4, 小鼠

Abstract: Objective The aim of this experiment was to investigate the effect of trimetazidine on the expression of NOX2 and NOX4 in liver tissues of mice with D-Galn/LPS-induced acute liver failure (ALF). Methods 65 male C57BL/6 mice were randomly divided into control, model, low-, moderate- and high-dose of trimetazidine, as wells as reduced glutathione-intervened group, 10 in each except for those (n=15) in the model. The ALF model was established by D-Galn/LPS intraperitoneal injection. The liver tissue homogenate malondialdehyde (MDA) and peroxidase (CAT) levels were detected, and hepatic NOX2/4 mRNA levels and protein expression were assayed by RT-PCR and Western blot. Results Serum ALT, AST and hepatic MDA levels in model group were (121.4±3.7)U/L,(208.9±27.4)U/L and (51.0±20.5)nmol/mg, all significantly higher than [(35.3±3.2)U/L, (49.9±4.4)U/L and (14.1±5.2) nmol/mg, P＜0.05] in the control, while hepatic CAT level was (51.7±16.8)U/mg, significantly lower than [(110.2±33.7)U/mg, P＜0.05] in the control; the hepatic NOX2/4 mRNA level and their protein expression in the model were (8.2±2.0)/(1.2±0.1) and (2.6±0.1)/(1.3±0.1), significantly higher than [(1.0±0.2)/(0.5±0.1) and (1.0±0.1)/(0.4±0.1), P＜0.05] in the control, serum ALT, AST and hepatic MDA levels in moderate- and high-dose trimetazidine-intervened groups were (86.4±1.00)U/L, (154.0±6.2)U/L and (22.5±1.9)nmol/mg, as well as (81.1±1.5)U/L, (134.7±5.3)U/L and (20.1±3.7)nmol/mg, significantly lower than [(121.4±3.7)U/L, (208.9±27.4)U/L and (51.0±20.5) nmol/mg, P＜0.05] in the model, hepatic CAT level were (99.4±15.5) and (102.3±15.5), significantly higher than [(51.6±16.8), P＜0.05] in the model; hepatic NOX2/4 mRNA levels and their protein expression were (5.6±0.2)/(0.7±0.0) and (5.2±1.4/0.6±0.1) as well as (1.7±0.2)/(0.7±0.2) and (1.5±0.1)/(0.6±0.2), significantly lower than [(8.2±2.0)/(1.2±0.1) and (2.6±0.1)/(1.3±0.1), P＜0.05] in the model. Conclusion Trimetazidine might inhibit the oxidative stress by down-regulation of hepatic NOX2/4 expression and improve the liver functions in D-Galn/LPS-induced mice.

Key words: Acute liver failure, Trimetazidine, Oxidative stress, NOX2, NOX4, Mice

汪娅, 罗婷婷, 李璨, 赵文静, 陆爽. 曲美他嗪对急性肝衰竭小鼠肝组织NOX2和NOX4表达的影响[J]. 实用肝脏病杂志, 2021, 24(6): 799-802.

Wang Ya, Luo Tingting, Li Can, et al. Effects of trimetazidine on the expression of NOX2 and NOX4 in liver tissues of mice with acute liver failure[J]. Journal of Practical Hepatology, 2021, 24(6): 799-802.

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