Abstract: Objective:To observe the effects of saponin of litchi seed (SL) on the oxidative stress and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in the impaired glucose regulation (IGR) rats,and to clarify their mechanisms. Methods:The IGR rat models were induced by high-fat feeding,then the rats were randomly divided into model group,metformin group (0.20 g·kg^-1),low dose of SL group (0.05 g·kg^<sup>-1),medium dose of SL group (0.1 g·kg^-1),and high dose of SL group (0.20 g·kg^-1); at the same time, normal control group was established; 12 rats in each group. After 6 weeks of administration,the effects of SL on the glucose and lipid metabolism were investigated. The expression levels of superoxide dismutase (SOD),malondialdehyde (MDA),HO-1 mRNA in pancreas tissue of the rats were observed by Real-time PCR,and the expression levels of whole cell HO-1 and Nrf2 in cytoplasm and nucleaus in pancreas tissue of the rats were decected by Western blotting method. The activity of SOD and the level of MDA in pancreas tissue of the rats were detected by the kits. Results: Compared with normal control group,the fasting blood glucose(FBG) and the blood lipid levels of the rats in model group were significantly increased (P<0.05 or P<0.01),the activity and mRNA expression level of SOD in pancreas tissue were decreased (P<0.01),the level and mRNA expression level of MDA were increased (P<0.01),the expression levels of Nrf2 protein in cytoplasm and nucleurs and the nucleur translaocation rate of Nrf2 were increased (P<0.01),and the mRNA and protein expression levels of HO-1 were upregualted (P<0.05 or P<0.01). Compared with model group,the FBG and serum TG levels in metformin group,medium and high doses of SL groups were decreased (P<0.05 or P<0.01),the activities and mRNA expression levels of SOD in pancreas tissue were increased (P<0.05 or P<0.01),the levels and mRNA expression levels of MDA were decreased (P<0.05 or P<0.01),the Nrf2 protein expression levels in cytoplasm were decreased (P<0.05 or P<0.01),the Nrf2 protein expression levels in nucleaus and the Nrf2 nucleaus translocation rates were increased (P<0.05 or P<0.01),and the mRNA and protein expression levels of HO-1 were upregualted (P<0.05 or P<0.01). Conclusion:SL can improve the glycolipid metabolism and has enhancement effect on anti-oxidative stress effect,and their mechanisms might be associated with activating the Nrf2/HO-1 signaling transduction pathway,promoting the nucleurs translocation of Nrf2 and increasing the expression of antioxidant gene in the down-stream such as HO-1.

Key words: impaired glucose regulation, oxidative stress, nuclear factor erythroid 2-related factor 2, saponin of litchi seed, heme oxygenase-1