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目的 研究长期口服1,6-二磷酸果糖(FDP)对不同的肝损伤模型的影响,探索口服FDP作为慢性肝损伤保护药物的可能性. 方法 用CCl4所致的肝损伤模型来观察FDP对慢性肝损伤的作用;用D-半乳糖(GalN)和脂多糖(LPS)所致的小鼠肝损伤模型来评价FDP对急性肝损伤的作用. 结果 在CCl4所致的大鼠慢性肝损伤模型中,FDP (1 - 4 g·kg-1·d-1 ig)连续用药10周,可明显降低血清中病理性升高的ALT、AST、γ-GT、T-BIL和ALP的含量,同时升高病理性降低的TP、ALB和T-CHO的水平;并明显降低肝组织中羟脯氨酸的含量;FDP 4.0 g·kg-1·d-1可明显减少肝硬化发生率和减轻肝组织病理改变.在GalN所致的小鼠急性肝损伤模型中,FDP 1.0 - 4.0 g·kg-1·d-1 (ig 3 d)显著降低血清中ALT和AST的水平(P＜0.01)和肝系数,4.0 g·kg-1·d-1可明显减轻肝细胞超微结构的病理性改变.在LPS所致的小鼠急性肝损伤模型中,FDP最大剂量(4.0 g·kg-1·d-1, ig 12 d)可明显降低血清中的ALT.结论 本研究首次证明了长期口服FDP对CCl4所致的慢性肝损伤具有保护作用,同时证实了它对急性肝损伤的保护作用,提示口服FDP对不同原因引起的肝损伤有效,有可能作为口服肝保护药用于临床.“,”Aim To investigate the effects of FDP on different liver injury models to explore the possibility of FDP used as an oral liver protective agent. Methods Chronic liver injury model in rats was induced by carbon tetrachloride (CCl4); Acute liver injury model in mice was induced by aminogalactose (GaIN) or lipopolysaccharide (LPS). Results In CCl4-induced chronic liver injury model, FDP (1 - 4 g·kg-1·d-1, q.d., for 10 weeks) significantly lowered ALT, AST, γ-glutamyl transpeptidase (γ-GT), alkaline phosphatase (ALP), and total bilirubin (T-BIL) in serum compared with vehicle; simultaneously it evidently elevated abnormal total protein (TP), albumin (ALB) and total cholesterol ( T-CHO ) levels in serum; it also dose-dependently reduced hydroxyproline contents in hepatic tissue. 4 g·kg-1·d-1 of FDP apparently decreased incidence of hepatic cirrhosis, and alleviated pathological changes of liver tissue. In GaIN-induced model, 1.0-4.0 g·kg-1·d-1 of FDP ( bid, for 3 d ) significantly lowered alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) levels in serum; it also decreased liver coefficient. 4.0 g·kg﹣1·d﹣1 of FDP significantly alleviated pathological changes of cell ultra-structures. In LPS-induced model, only high dose of FDP (4.0 g·kg﹣1·d﹣1, bid, for 12 d) significantly decreased ALT level in serum. Conclusion This study first demonstrated the protective effect of oral FDP on chronic liver injury caused by CCl4, and confirmed its effect on acute liver injury at the same time, suggesting that Long-term oral FDP is efficacious against liver injury induced by different factors and can be used as an oral liver protective agent in clinic.