急性肝衰竭（ALF）是短时间内大量肝细胞的凋亡和坏死，其发病机制尚未完全阐明。过氧化物酶体增殖物激活受体α（PPARa）参与了细胞脂质代谢、炎症、分化及凋亡等反应。内质网应激（ERS）是错误折叠或未折叠的蛋白质在内质网腔内聚集的一种亚细胞器的病理状态。前期研究发现在小鼠ALF进展过程中，PPARa表达进行性减少，激活PPARa能减轻ALF诱导的ERS和细胞凋亡。本研究将在小鼠ALF模型上应用PPARa激动剂Wy-14,643，研究PPARa和ERS诱导的细胞凋亡在ALF发生发展中的作用，为进一步研究PPARa/ERS间的相互作用及分子机制奠定基础。

Acute liver failure (ALF) is characterized by extensive hepatic apoptosis and necrosis developed rapidly. Although the nature of ALF has been extensively studied, the pathogenesis is still unclear. Peroxisome proliferator-activated receptor alpha (PPARa) is a ligand-activated nuclear transcription factors, which has been reported to regulate lipid metabolism, inflammation, differentiation and apoptosis, etc. Endoplasmic reticulum stress (ER stress) is induced by physiological and/or pathological stress signals, leading to the accumulation of unfolded or misfolded proteins in the ER. We have demonstrated that PPARa was suppressed during ALF progression and PPARa activation decreased ER stress and hepatocyte apoptosis. Thus, in the present study, we use Wy-14,643 to activate PPARa. In order to explore the mechanism of PPARa and ER sress-induced hepatocyte apoptosis in the progression of ALF, we evaluate their changes in a D-galactosamine (D-GalN) and lipopolysaccharide (LPS) induced mouse model.

急性肝衰竭（ALF）是短时间内大量肝细胞的凋亡和坏死，其发病机制尚未完全阐明。过氧化物酶体增殖物激活受体α（PPARα）参与了细胞脂质代谢、炎症、分化及凋亡等反应。内质网应激（ER stress）是错误折叠或未折叠的蛋白质在内质网腔内聚集的一种亚细胞器的病理状态。我们前期的研究已经证实ALF时PPARα表达受抑，本研究在腹腔注射D-氨基半乳糖（D-GalN）/脂多糖（LPS）建立的小鼠ALF模型中发现肝细胞凋亡增加，应用PPARα激动剂Wy-14643后肝细胞的凋亡减少 ( P<0.01)，ER stress的标志物Grp78、Grp94、CHOP mRNA（分别为 0.63±0.36、0.46±0.29、3.85±1.25）和蛋白（分别为0.67±0.05、0.31±0.05、0.18±0.02）较ALF模型组明显减少（P均<0.05），从而对ALF产生保护作用，为进一步研究PPARα/ERS间的相互作用及分子机制奠定基础。