线粒体是急性肝衰竭（ALF）炎症反应和细胞死亡的中枢：在胞内合成ATP充足，则细胞凋亡，引发低水平炎性DAMPs及轻度炎症；反之则胀亡，引发高水平炎性DAMPs及重度炎症。新近发现，PPARα通过调控UCP2解偶联来干预ATP合成而调节细胞死亡的方式。前期研究发现：四逆加人参汤（SNRS）能改善HBV-ACLF晚期生化指标、显著提高患者生存率、改善实验动物凋亡及胀亡信号。提出：“SNRS经PPARα/UCP2途径干预线粒体ATP合成及炎性DAMPs，减少肝细胞胀亡，阻断随之引发的瀑布式炎症反应，以降低ALF病死率”。现拟验证SNRS对ALF的疗效、线粒体结构、ATP合成及肝细胞死亡方式的影响；用激动剂、抑制剂及siRNA干扰等手段，在体内、体外确证SNRS经PPARα/UCP2干预ATP合成的机理，以阐明SNRS “固脱救逆”挽救ALF的关键分子事件，并为中医治疗其它急重症的研究提供范示。

Mitochondria are the central axis of acute liver failure (ALF) inflammatory responses and cell death: When ATP synthesis is sufficient, apoptotic cells were predominant,triggering low levels of inflammation. Conversely, high levels of inflammatory responses are triggered after oncosis.It has recently been discovered that PPARα regulates the uncoupling process of UCP2 to interfere with ATP synthesis, thereby regulating cell death patterns. Previous studies found that Sini Decoction plus Ginseng Soup(SNRS) could improve the late symptoms and biochemical markers, block the process of severity, significantly improve the survival rate of patients with Hepatitis B Virus related acute-on-chronic liver failure (HBV-ACLF),and animal experiments have found that it significantly influence signaling pathway related to both apoptosis and oncosis. So we propose the hypothesis that SNRS can influence the mitochondria associated PPARα/UCP2 signaling pathway, regulate ATP synthesis and DAMPs, reduce hepatocyte oncosis, and inhibit cascade of proinflammatory reactions. To verify the effect of SNRS on ALF, mitochondrial structure, ATP synthesis and hepatocyte death mode, we used agonists, inhibitors and siRNA interference to confirm it in vivo and in vitro that SNRS interferes with key molecular events of ATP via PPARα/UCP2 pathway. The purpose of this study is to elucidate the molecular mechanism of “consolidate and resuscitate collapse” for saving ALF by SNRS,and to provide a model for similar studies of treating critically ill by traditional Chinese medicine.