Effect Of Gross Saponins From Tribulus Terrestrisl On Hepatic Apoptosis In Mice's Acute Hepatic Injury Induced By Tripterygium Glycosides

Objective:To confirm the protectant mechanism of gross saponins from tribulus terrestrisl on mice induced acute hepatic injury by tripterygium glycosides,and explore its influence to the hepatic apoptosis.Methods:60 mice of Kunming-strain were randomly divided into blank control group,positive group,model group,big-dosage,medium-dosage and small-dosage group of gross saponins from tribulus terrestrisl.Before establishing models,big-dosage, medium-dosage and small-dosage group were respectively perfused with the dosage of 1.36g/㎏ ,0.68g/㎏ and 0.34g/㎏ for successive 7 days. Positive group was administered by Ganlixin capsule with the dosage of 0.075g/kg. Simultaneously,blank control group and model group were given equivoluminal distilled water. 12 hours after the last dosage, all groups were perfused once to make model with the dosage of 0.27g/kg 0.2mL/10g of tripterygium glycosides except for blank control model. 18 hours after ,the 1evels of ALT ,AST,SOD,MDA and GSH-Px in the serum were measured and pathological morphology of the liver tissue under light microscope,liver cell ultrastucture under electronic microscope and liver cell apoptosis by using the method of TUNEL were observed. Caspase-3 were also observed by using the method of immunohistochemical method.Results:(1) Hepatic function change: the level of ALT and AST in the serum of model group rised obviously . Compared with model group, each dosage of gross saponins from tribulus terrestrisl could reduce it obviously(P<0.05),especially in big-dosage and medium-dosage groups of gross saponins from tribulus terrestrisl; (2) Lipid peroxidation of free radical: Compared with blank control group ,SOD and GSH-Px in the model group decreased and MDA rised obviously(P<0.05) ,Compared with blank control group,each dosage of groups and Ganlixin group could obviously improve SOD and GSH-Px,reduce MDA in the serum, Big-dosage of gross saponins from tribulus terrestrisl was the most effective one; (3) Pathology change: Compared with model group,each dosage of groups could ameliorate the injured liver cells in different level(P<0.05). Big-dosage of gross saponins from tribulus terrestrisl was the most effective one; (4) Ultrastructure change: the ultrastucture of the liver cell of model group had obvious change, each dosage of groups could ameliorate the ultrastucture of the liver cell in different level(P<0.05). (5) Apoptosis: Compared with blank control group,the mice in model group appeared to be apoptosis of liver cell(P<0.05), each dosage of groups and Ganlixin showed great effect on restraining the apoptosis; (6) Caspase-3 expression: Compared with blank control group, the expression of Caspase-3 in the serum of model group increased obviously(P<0.05). Compared with model group,the expression of Caspase-3 could be degraded in each dosage of groups(P<0.05), Big-dosage of gross saponins from tribulus terrestrisl and Ganlixin groups were most obvious.Conclusions: (1) Gross saponins from Tribulus terrestrisl has the effects of liminating pathologic heat,damp and detoxification,adjusting the liver and strengthening the spleen and stomach ,can effectively prevent and treat DILI. (2) Lipid peroxidation of free radical and apoptosis induced by tripterygium glycosides is one of the pathological mechanism of acute hepatic injury. (3) Gross saponins from Tribulus terrestrisl can ameliorate the injured liver cells in different levels. (4) The mechanism of its protective effective effect may be related to the antioxidant activity and the influence on regulate metabolism,as well as repressing apoptosis of the liver cells,effectively reduce the level of Caspase-3.