摘要
目的:探讨甲基莲心碱(Nef)对对乙酰氨基酚(APAP)所致肝损伤的改善作用及可能机制。方法:将50只小鼠随机分为0.9%氯化钠溶液(NS)对照组、APAP+NS组、APAP+Nef(5)组、APAP+Nef(10)组和APAP+Nef(20)组,每组10只。APAP+Nef(5)组、APAP+Nef(10)组和APAP+Nef(20)组均给予400 mg/kg APAP建立药物性肝损伤(DILI)模型,Nef剂量为5、10、20 mg/kg,其余两组以等量0.9%氯化钠溶液替代Nef进行灌胃处理。分析Nef对APAP诱导的肝功能和形态学损伤、氧化应激反应、炎症反应、细胞凋亡及Nrf2相关抗氧化信号通路的影响。结果:与NS对照组比较,APAP+NS组丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、IL-10、3-硝基酪氨酸(3-NT)和诱导型一氧化氮合酶(iNOS)水平以及B细胞淋巴瘤因子-2(Bcl-2)相关蛋白X(Bax)和裂解型半胱氨酸蛋白酶-3(Cleaved caspase-3)蛋白表达升高,超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-Px)水平降低,Bcl-2蛋白表达降低,核因子-红细胞2相关因子2(Nrf2)、血红素加氧酶1(HO-1)、NAD(P)H醌脱氢酶1(NQO1)mRNA和蛋白表达降低,肝组织病理损伤加重(均P<0.05)。与APAP+NS组比较,APAP+Nef(10)组和APAP+Nef(20)组上述指标改善,肝组织病理损伤减轻,且APAP+Nef(20)组优于APAP+Nef(10)组(均P<0.05)。结论:Nef能够改善APAP诱导的肝损伤,其机制可能为通过上调Nrf2/HO-1/NQO1信号通路抑制氧化应激反应。
Objective:To explore the improvement effect and possible mechanism of Nef on liver injury induced by acetaminophen(APAP).Methods:A total of 50 mice were randomly divided into NS control group,APAP+NS group,APAP+Nef(5)group,APAP+Nef(10)group and APAP+Nef(20)group,with 10 mice in each group.The APAP+Nef(5)group,APAP+Nef(10)group and APAP+Nef(20)group were all given 400 mg/kg APAP to establish drug-induced liver injury(DILI)models,with Nef doses of 5,10 and 20 mg/kg.The other two groups were treated with an equal amount of 0.9%sodium chloride solution instead of Nef by gavage.The effects of Nef on APAP induced liver function and morphological damage,oxidative stress response,inflammatory response,cell apoptosis and Nrf2 related antioxidant signaling pathways were analyzed.Results:Compared with the NS control group,the APAP+NS group showed increased levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-10,3-nitrotyrosine(3-NT)and inducible nitric oxide synthase(iNOS),as well as increased protein expression of B cell lymphoma factor-2(Bcl-2)-related protein X(Bax)and Cleaved caspase-3,decreased levels of superoxide dismutase(SOD),glutathione(GSH)and glutathione peroxidase(GSH-Px),decreased protein expression of Bcl-2,and the mRNA and protein expressions of nuclear factor erythroid 2 related factor 2(Nrf2),hemeoxygenase-1(HO-1)and NAD(P)H quinone dehydrogenase 1(NQO1)decreased,and the pathological damage to liver tissue worsened(all P<0.05).Compared with the APAP+NS group,the APAP+Nef(10)group and APAP+Nef(20)group showed a improvement in the above indicators and a reduction in liver tissue pathological damage,and the APAP+Nef(20)group was superior to the APAP+Nef(10)group(all P<0.05).Conclusion:Nef can improve APAP induced liver injury,possibly by up-regulating the Nrf2/HO-1/NQO1 signaling pathway to inhibit oxidative stress response.
作者
冯阳
施京红
蒲柯
罗婷
丁辉
FENG Yang;SHI Jinghong;PU Ke;LUO Ting;DING Hui(The Affiliated Hospital of Northwest University,Xi’an 710018,China;Shaanxi University of Chinese Medicine,Xianyang 712046,China;The Affiliated Hospital of North Sichuan Medical College,Nanchong 637000,China;Shaanxi Academy of Traditional Chinese Medicine,Xi’an 710003,China)
出处
《陕西医学杂志》
2025年第9期1161-1169,1207,共10页
Shaanxi Medical Journal
基金
国家自然科学基金资助项目(82204877)。
