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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-1ig)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。
Objective To investigate the effect of long-term oral administration of fructose-1,6-diphosphate (FDP) on different liver injury models and to explore the possibility of oral FDP as a protective drug against chronic liver injury. Methods The liver injury model induced by CCl4 was used to observe the effect of FDP on chronic liver injury. The effect of FDP on acute liver injury was evaluated by the model of liver injury induced by GalN and lipopolysaccharide (LPS) . Results The continuous administration of FDP (1 -4 g · kg-1 · d-1ig) for 10 weeks in CCl4-induced chronic liver injury model significantly reduced the pathological elevation of serum ALT, AST, γ- GT, T-BIL and ALP, and elevated the levels of pathologically reduced TP, ALB and T-CHO, as well as significantly reduced the content of hydroxyproline in liver tissue. FDP 4.0 g · kg -1 · d- 1 can significantly reduce the incidence of liver cirrhosis and reduce the pathological changes of liver tissue. In the model of acute liver injury induced by GalN, FDP 1.0 -4.0 g · kg-1 · d-1 (ig for 3 d) significantly decreased the serum ALT and AST levels (P <0.01) g · kg-1 · d-1 can significantly reduce the pathological changes of liver cell ultrastructure. In the acute liver injury model induced by LPS, the maximum dose of FDP (4.0 g · kg-1 · d-1, ig for 12 d) could significantly reduce the serum ALT. Conclusions This study, for the first time, demonstrates that long-term oral FDP has a protective effect against chronic liver injury induced by CCl4 and at the same time it has demonstrated its protective effect against acute liver injury, suggesting that oral FDP is effective for liver damage caused by different causes and may be used as oral liver Protective drugs for clinical use.