摘要
非酒精性脂肪性肝病(NAFLD),尤其是非酒精性脂肪性肝炎(NASH)已成为肝移植和肝相关性死亡的主要原因。然而,NASH的发病机制仍不清楚。目前,还没有FDA批准的药物来治疗这种疾病。AMP依赖的蛋白激酶(AMPK)可以感知能量状态并调节代谢过程以维持体内平衡。AMPK的活性受到碳水化合物、脂肪和氨基酸等营养物质的调节。AMPK活性因营养缺乏而增加,但在肥胖期间因营养过剩、炎症和某些合成代谢激素(如胰岛素)的过度分泌而受到抑制。抑制肝脏AMPK活性可以使其从单纯性脂肪变性转变为肝细胞死亡,因此激活AMPK可能改善NASH的相关症状。
Nonalcoholic fatty liver diseases (NAFLD), especially nonalcoholic steatohepatitis (NASH), have become a major cause of liver transplant and liver-associated death. However, the pathogenesis of NASH is still unclear. Currently, there is no FDA-approved medication to treat this devastating disease. AMP-activated protein kinase (AMPK) senses energy status and regulates metabolic processes to maintain homeostasis. The activity of AMPK is regulated by the availability of nutrients, such as carbohydrates, lipids and amino acids. AMPK activity is increased by nutrient deprivation, and inhibited by overnutrition, inflammation and hypersecretion of certain anabolic hormones, such as insulin, during obesity. The repression of hepatic AMPK activity permits the transition from simple steatosis to hepatocellular death, and thus activation might ameliorate multiple aspects of NASH. Here, we review the pathogenesis of NAFLD and the impact of AMPK activity state on hepatic steatosis, inflammation, liver injury and fibrosis during the transition of NAFL to NASH and liver failure.
出处
《药物资讯》
2023年第3期224-232,共9页
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