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Abstract：
BACKGROUND: Endoplasmic reticulum (ER) stress, promoting lipid metabolism disorders and steatohepatitis, contributes significantly to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Hugan Qingzhi tablets (HQT) has a definite effect in the clinical treatment of NAFLD patients, but its mechanism is still unclear. This study aims to investigate the effects of HQT on ER stress in the liver tissues of NAFLD rats and explore the underlying mechanism.
METHODS: The NAFLD rat model was managed with high-fat diet (HFD) for 12weeks. HQT was administrated in a daily basis to the HFD groups. Biochemical markers, pro-inflammatory cytokines, liver histology were assayed to evaluate HQT effects in HFD-induced NAFLD rats. Furthermore, the expression of ER stress-related signal molecules including glucose regulating protein 78 (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), p-PERK, eukaryotic translation initiation factor 2α (EIF2α), p-EIF2α, activating transcription factor 4 (ATF4), acetyl-coenzyme A-carboxylase (ACC), activating transcription factor (ATF6), and nuclear factor-kappa B-p65 (NF-κB-p65) were detected by western blot and/or qRT-PCR.
RESULTS: The histopathological characteristics and biochemical data indicated that HQT exhibited protective effects on HFD-induced NAFLD rats. Furthermore, it caused significant reduction in the expression of ERS markers, such as GRP78, PERK, p-PERK, and ATF6, and subsequently downregulated the expression of EIF2α, p-EIF2α ATF4, ACC, and NF-κB-p65.
CONCLUSIONS: The results suggested that HQT has protective effect against hepatic steatosis and inflammation in NAFLD rats by attenuating ER stress, and the potential mechanism is through inhibition of PERK and ATF6 pathways.
METHODS: The NAFLD rat model was managed with high-fat diet (HFD) for 12weeks. HQT was administrated in a daily basis to the HFD groups. Biochemical markers, pro-inflammatory cytokines, liver histology were assayed to evaluate HQT effects in HFD-induced NAFLD rats. Furthermore, the expression of ER stress-related signal molecules including glucose regulating protein 78 (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), p-PERK, eukaryotic translation initiation factor 2α (EIF2α), p-EIF2α, activating transcription factor 4 (ATF4), acetyl-coenzyme A-carboxylase (ACC), activating transcription factor (ATF6), and nuclear factor-kappa B-p65 (NF-κB-p65) were detected by western blot and/or qRT-PCR.
RESULTS: The histopathological characteristics and biochemical data indicated that HQT exhibited protective effects on HFD-induced NAFLD rats. Furthermore, it caused significant reduction in the expression of ERS markers, such as GRP78, PERK, p-PERK, and ATF6, and subsequently downregulated the expression of EIF2α, p-EIF2α ATF4, ACC, and NF-κB-p65.
CONCLUSIONS: The results suggested that HQT has protective effect against hepatic steatosis and inflammation in NAFLD rats by attenuating ER stress, and the potential mechanism is through inhibition of PERK and ATF6 pathways.
摘要：
背景：内质网（ER）应激，促进脂质代谢紊乱和脂肪性肝炎，非酒精性脂肪性肝病(NAFLD)的发病机制有重要作用。护肝清脂片(HQT)在NAFLD患者的临床治疗中疗效确切,但其机制尚不清楚。本研究旨在探讨HQT对NAFLD大鼠肝组织内质网应激的影响及其机制。
方法：NAFLD大鼠模型采用高脂饮食（HFD）处理12周。每天向HFD组施用HQT。生化标志物,促炎细胞因子，对HFD诱导的NAFLD大鼠进行肝组织学分析以评估HQT效应。此外，内质网应激相关信号分子包括葡萄糖调节蛋白78（GRP78）的表达，蛋白激酶RNA样内质网激酶（PERK），p-PERK,真核翻译起始因子2α（EIF2α），p-EIF2α,激活转录因子4（ATF4），乙酰辅酶A羧化酶（ACC），激活转录因子（ATF6），通过蛋白质印迹和/或qRT-PCR检测核因子-κB-p65（NF-κB-p65）。
结果：组织病理学特征和生化数据表明HQT对HFD诱导的NAFLD大鼠具有保护作用。此外，它导致ERS标记表达的显著减少，如GRP78，PERK，p-PERK,和ATF6，随后下调了EIF2α的表达，p-EIF2αATF4,ACC,和NF-κB-p65。
结论：结果表明，HQT通过减轻ER应激对NAFLD大鼠肝脏脂肪变性和炎症具有保护作用，潜在的机制是通过抑制PERK和ATF6途径。
方法：NAFLD大鼠模型采用高脂饮食（HFD）处理12周。每天向HFD组施用HQT。生化标志物,促炎细胞因子，对HFD诱导的NAFLD大鼠进行肝组织学分析以评估HQT效应。此外，内质网应激相关信号分子包括葡萄糖调节蛋白78（GRP78）的表达，蛋白激酶RNA样内质网激酶（PERK），p-PERK,真核翻译起始因子2α（EIF2α），p-EIF2α,激活转录因子4（ATF4），乙酰辅酶A羧化酶（ACC），激活转录因子（ATF6），通过蛋白质印迹和/或qRT-PCR检测核因子-κB-p65（NF-κB-p65）。
结果：组织病理学特征和生化数据表明HQT对HFD诱导的NAFLD大鼠具有保护作用。此外，它导致ERS标记表达的显著减少，如GRP78，PERK，p-PERK,和ATF6，随后下调了EIF2α的表达，p-EIF2αATF4,ACC,和NF-κB-p65。
结论：结果表明，HQT通过减轻ER应激对NAFLD大鼠肝脏脂肪变性和炎症具有保护作用，潜在的机制是通过抑制PERK和ATF6途径。
