Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
Lipids Health Dis. 2011 Dec 30;10:246. doi: 10.1186/1476-511X-10-246.
Peroxisome proliferator activated receptor alpha (PPARα) regulates lipids metabolism and inhibits inflammatory response. However, the role of PPARα in alcoholic liver disease is largely unknown. We aim to elucidate the effect and the molecular basis of PPARα in ethanol induced hepatic injury in mice.
C57BL/6J mice fed with 4% ethanol-containing Lieber-DeCarli liquid diet for 12 weeks exhibited hepatocyte steatosis, necrosis and inflammatory infiltration, accompanied with elevated serum alanine aminotransferase (ALT) and aspartic transaminase (AST) levels, decreased hepatic expression of PPARα, lipids oxidation promoting genes and anti-inflammatory factors, as well as enhanced hepatic expression of fatty acids synthesis promoting genes and pro-inflammatory cytokines. Induction of PPARα by PPARα agonist WY14643 treatment for 2 weeks ameliorated the severity of liver injury and restored expression of genes altered by ethanol treatment. However, administration of PPARα antagonist GW6471 for 2 weeks promoted the inflammatory response.
The present study provided the evidence for the protective role of PPARα in ameliorating ethanol induced liver injury through modulation of the genes related to lipid metabolism and inflammatory response.
过氧化物酶体增殖物激活受体α（PPARα）调节脂质代谢并抑制炎症反应。然而，PPARα 在酒精性肝病中的作用在很大程度上尚不清楚。我们旨在阐明 PPARα 在乙醇诱导的小鼠肝损伤中的作用及其分子基础。
用含 4%乙醇的 Lieber-DeCarli 液体饮食喂养 12 周的 C57BL/6J 小鼠表现出肝细胞脂肪变性、坏死和炎症浸润，伴随着血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平升高，肝内 PPARα、促进脂质氧化的基因和抗炎因子表达降低，以及促进脂肪酸合成的基因和促炎细胞因子表达增强。PPARα 激动剂 WY14643 诱导 2 周可改善肝损伤严重程度，并恢复乙醇处理改变的基因表达。然而，PPARα 拮抗剂 GW6471 给药 2 周可促进炎症反应。
本研究提供了证据表明，通过调节与脂质代谢和炎症反应相关的基因，PPARα 在改善乙醇诱导的肝损伤中发挥保护作用。
