肝源性糖尿病（HD）发病广、危害重,但其病理机制尚不明确,缺乏有效防治手段。基于肝糖异方有效改善HD的前期基础,及Nrf2信号通路和氧化应激在HD病理中的研究进展,我们提出“肝糖异方重在调节Nrf2信号通路、改善肝细胞氧化应激损伤，并抑制活化肝星状细胞对肝细胞的炎性损伤，从而改善肝细胞胰岛素抵抗、促进其糖原合成与减少糖异生，发挥防治肝源性糖尿病的效应；其中，实脾中药在上调Nrf2信号通路中发挥主要作用”的科学假说。复制氧化应激损伤大鼠体内外模型,分别以肝糖异方及其拆方干预，体外并以Nrf2的沉默siRNA或激动剂为对照,观察肝组织损伤、纤维化、胰岛素抵抗、糖原合成与糖异生，尤其是Nrf2及其下游效应通路的变化。再观察各组药物血清与活化的星状细胞共培养后的条件培养液对肝细胞损伤、糖原含量、凋亡的影响。从而阐明肝糖异方防治HD的关键药理机制，并明确实脾治法作用特点，为中医药防治HD提供新思路。

Although hepatogenous diabetes (HD) has high incidence rate and poor prognosis in chronic liver disease, its pathological mechanism is still unclear and the effective prevention and treatment means are absent. Based on the previous work that Chinese herbal compound (Gantangyi recipe) have good curative effects on HD and that the Nrf2 signal pathways and oxidative stress (OS) play important roles in HD pathological change, we hypothesize that Gantangyi recipe can relieve oxidative stress damage and insulin resistance of hepatocyte cell (HC), inhibit the inflammatory damage of activated hepatic stellate cells (HSC) to HC by regulating Nrf2 signaling pathways, thus exerts therapeutic effects by promoting the glycogen synthesis and reducing gluconeogenesis. And the spleen-firming herbal therapy shows its main influence by up-regulating the Nrf2 signal pathways. The cirrhotic rat model in vivo and the HC in vitro which characterized by oxidative stress damage are set up and treated with Gantangyi recipe and its component recipe or their pharmacologic serum. In vitro, the siRNA or agonist of Nrf2 was transfected or added to the culture BRL HC as control or culture condition. The oxidative damage, fibrosis, insulin resistance, glycogen synthesis and gluconeogenesis of hepatic tissue were observed. Meanwhile, the changes of signal pathway of Nrf2 and its downstream signal pathways were observed too. The pharmacologic serum of each group was cultured with the activated HSC caused by lipopolysaccharide, then this conditioned medium was added to damage the HC, and the impacts of oxidative damage, glycogen contents, and apoptosis of HC were observed. Then to clarify the key pharmacological mechanisms of Gantangyi recipe on treating HD, to illustrate the effect characteristics of the spleen-firming herbal therapy, to provide a new way of prevention and treatment for HD by traditional Chinese medicine.