高脂血症是心脑血管等众多疾病的病理基础。我们研制的重组SAK-HV可显著降低ApoE-/-小鼠血胆固醇和甘油三酯，并改善肝脏脂肪沉积。其降脂效果显著优于上市药物阿托伐他汀。研究发现给药组血IL-6升高，肝脏温和增殖，Stat3和C/ebpβ活化，雌激素升高。同时肝脏转录组分析表明脂质氧化以及类固醇激素合成上调，并提示pgc1a可能是SAK-HV降脂效应的关键蛋白。抑制Stat3和敲低Pgc-1α进一步证实它们直接参与了SAK-HV的快速降脂过程，但其详细作用机制未知。我们拟基于肝脏转录组分析设计试验，通过基于抑制剂或基因敲低、敲除的一系列体内外实验深入研究SAK-HV的降脂机制。本研究有望为高脂血症治疗提供新靶点，为安全高效的降脂候选药物研制奠定基础。

Hyperlipemia is the pathogenesis of many diseases, including cerebral-cardio vascular diseases. Recombinant SAK-HV developed by us significantly decreased the serum cholesterol and triglyceride, and improved hepatic steatosis in ApoE-/- mice. Its lipids-lowering effect was significantly better than that of the post-market drug atorvastatin. We found that SAK-HV triggered moderate liver proliferation, accompanied with upregulation of serum IL-6 and activation of both STAT3 and C/ebpβ in liver, as well as the increment of hepatic estrogen level. Meanwhile, the liver transcriptome analysis identified upregulation of both lipids oxidation and hormone synthesis, and further suggested that Pgc-1α was the key effector of the lipid-lowering effect of SAK-HV. Both STAT3 inhibition and Pgc-1α knockout further verified that the direct involvement of STAT3 and Pgc-1α in the rapid lipid-lowering process of SAK-HV. However, the detailed mechanism is unclean. We planed to design experiments based on the liver transcriptome analysis, and make an intensive study about the lipid-lowering mechanism of SAK-HV via a series of experiments based on inhibitors, gene knockout and knock down both in vivo and in vitro. Our research may provide new targets for the treatment against hyperlipemia, and establish foundation for the development of safe and efficient lipid-lowering candidate drugs.