目的:非酒精性脂肪性肝病(NAFLD),包括非酒精性脂肪性肝炎(NASH),胰十二指肠切除术(PD)后可能发生。然而,NASH发展的机制尚不清楚。这项研究旨在检查与PD后NASH发生相关的基因表达变化。
方法:使用7例PD后NASH患者的肝脏样本检测与脂肪酸/甘油三酯(FA/TG)代谢和炎症信号相关的基因表达,并与6例健康个体和32例常规NASH患者进行比较。
结果:PD后NASH患者的肝脏显示出编码CD36,FA结合蛋白1和4,乙酰辅酶A羧化酶α的基因显着上调,与正常和常规NASH肝脏相比,二酰基甘油酰基转移酶2和过氧化物酶体增殖物激活受体(PPAR)γ。尽管PD后NASH患者的血清载脂蛋白B(ApoB)和TG降低,ApoB和微粒体TG转移蛋白的mRNA强烈增加,表明肝脏的TG输出受损,为极低密度脂蛋白(VLDL)。此外,PD后NASH肝脏中髓样分化原发反应88和超氧化物歧化酶的mRNA水平升高提示先天免疫反应显著激活和氧化应激产生增强.
结论:增强肝细胞对FA的摄取和脂肪生成,PPARγ的上调,和VLDL排泄到循环中的破坏是PD后脂肪生成的可能机制。
结论:这些结果为了解PD后NAFLD/NASH的发病机制提供了基础。
OBJECTIVE: It is recognized that nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), may develop after pancreaticoduodenectomy (PD). However, the mechanism of NASH development remains unclear. This study aimed to examine the changes in gene expression associated with NASH occurrence following PD.
METHODS: The expression of genes related to fatty acid/triglyceride (FA/TG) metabolism and inflammatory signaling was examined using liver samples obtained from 7 post-PD NASH patients and compared with 6 healthy individuals and 32 conventional NASH patients.
RESULTS: The livers of post-PD NASH patients demonstrated significant up-regulation of the genes encoding CD36, FA-binding proteins 1 and 4, acetyl-coenzyme A carboxylase α, diacylglycerol acyltransferase 2, and peroxisome proliferator-activated receptor (PPAR) γ compared with normal and conventional NASH livers. Although serum apolipoprotein B (ApoB) and TG were decreased in post-PD NASH patients, the mRNAs of ApoB and microsomal TG transfer protein were robustly increased, indicating impaired TG export from the liver as very-low-density lipoprotein (VLDL). Additionally, elevated mRNA levels of myeloid differentiation primary response 88 and superoxide dismutases in post-PD NASH livers suggested significant activation of innate immune response and augmentation of oxidative stress generation.
CONCLUSIONS: Enhanced FA uptake into hepatocytes and lipogenesis, up-regulation of PPARγ, and disruption of VLDL excretion into the circulation are possible mechanisms of steatogenesis after PD.
CONCLUSIONS: These results provide a basis for understanding the pathogenesis of NAFLD/NASH following PD.