前期证实祛湿化瘀方（QHD）对非酒精性脂肪性肝病（NAFLD）疗效显著，并可显著抑制NAFLD模型鼠肝细胞固醇调节元件结合蛋白1（SREBP-1）表达。结合新近所阐明的“半胱天冬酶2（Caspase2）切割位点1蛋白酶（S1P）可触发SREBPs持续活化，促进NAFLD进展”的机制，提出“祛湿化瘀方可能通过Caspase2抑制SREBP-1活化从而改善非酒精性脂肪肝肝脏脂肪沉积”的科学假说。设立QHD高、中、低剂量组，采用高脂饮食诱导小鼠NAFLD模型，设Caspase2抑制剂作对照；采用游离脂肪酸诱导的肝细胞脂肪变性模型及Caspase2基因沉默细胞模型，设Caspase2抑制剂、Caspase2正常表达肝细胞株作对照，围绕Caspase2/SREBP-1及SREBP-1下游脂肪合成的相关通路，探讨QHD是否通过抑制Caspase2进而抑制SREBP-1的活化从而防治NAFLD。

The research group initially screened out that Qushi Huayu Decoction (QHD) had a significant effect on nonalcoholic fatty liver disease (NAFLD), and found that QHD could significantly inhibit the expression of SREBP-1 in NAFLD model rats. Based on the recently clarified mechanism that Caspase 2 cleavage site 1 protease (S1P) can trigger the sustained activation of SREBPs and promote the progress of NAFLD, the scientific hypothesis that QHD may improve the hepatic fat deposition in nonalcoholic fatty liver by regulating Caspase2 and inhibiting the sustained activation of SREBP-1 is proposed.The NAFLD model will be induced by high-fat diet, and QHD high, medium and low dose groups to be set up, Caspase2 inhibitors used as control group. Free fatty acid-induced steatosis model of hepatocytes and Caspase2 gene silencing cell model of hepatocytes will be used, and Caspase2 inhibitors and normal Caspase2 expression cell lines used as control, focusing on the Caspase2/SREBP-1 and the related pathways of increasing fat synthesis after the continuous activation of SREBP-1, to explore whether QHD can inhibit the activation of SREBP-1 by regulating Caspase2 and thereby inhibit the progress of NAFLD, and to elucidate the pharmacological mechanism and possible targets of QHD in the treatment of NAFLD.