Tripterygium Glycosides Induced Liver Injury - Effect Relationship, "the Study Of Free The Immunotoxin Management Mechanism

Objective:To reserch the relationship between time and effect of immunotoxicology in the liver of SD rat with the clinical dosage of Tripterygium Glycosides,and to study the recovery of the injuried liver at intervals.Methods:The model rats were intragastric administration with clinical dosage of Tripterygium Glycosides,the rat were divided into five groupes based on different times.To detect the general state of health and the basic immunological index inculding:body weight,index number of the liver,thymus and spleen;The glutamic-pyruvic transaminase(GPT/ALT) and the glutamic-oxal(o)acetic transaminase,(GOT/AST);immune activity cells(natural killer cell,T-cell and B-cell activity )function were investigated too.Immunohistochemistry technique was employed to study the CD₆₈ antigen at the macrophage and Fas expression in liver, through ELISA to investigate the TNF-αin the homogenate of liver and use the flow cytometer to detection the apoptosis index of the liver cell cycle and Fas expression heptocyte,to analyze the concentration of Ca²⁺ in the liver with confocal microscope.In order to approach the clinical dosage of Tripterygium Glycosides induction the liver injured mechanism,the results incorporate with the time-effect relationship,At the same time,we also do the observation of injury groups,and investigate the convalescent period of injury groups.Reslut:1.The weight of experimental groups decreased significantly(p＜0.05),the index number of the liver increased in the 5th group(p＜0.05),spleen decreased in the 5th group(p＜0.05),and the index number of the thymus decreased(p＜0.05) too;The glutamic-pyruvic transaminase(GPT/ALT) increased(p＜0.05) at the 5th week;The glutamic-oxal(o)acetic transaminase,(GOT/AST) increased(p＜0.05) at the 4th week, and increased signifcantly(p＜0.01) at the 5th week.HE showed the hepatocyte began to loss the original structure,even with swollen,necrosis,vacuolar degeneration, thrombus,fatty degeneration,apoptotic body and inflritation of netrophlic cell and lymphcyte from the 3nd week,obviously at the 5th week.2.The activity of NK decreased(p＜0.05) at the 4th and 5th week in the experimental group;the proliferation of experimental T and B cell decreased(p＜0.05) at 4th week; and decreased signifcantly(p＜0.01) at the 5th week.3.The expression of the CD₆₈ in the liver Kupffer cell increased(p＜0.05) at the 3nd and 4th week,signifcantly(p＜0.01) in the 5th week.The expression of the TNF-αin the liver increased(p＜0.05) at the 4th week,signifcantly(p＜0.01) in the 5th week;The expression of Fas in liver increased(p＜0.05) at the 4th week, signifcantly(p＜0.01) at the 5th week;The expression of Ca²⁺ and apoptosis index of liver cells increased(p＜0.05) at the 4th week,signifcantly(p＜0.01) at the 5th week.4.The liver function of the 4th and 5th group are almost normal(p＞0.05),and morphology of liver are closed to normal too.Conclusion:1.The weight,index of organ,the liver function and the pathomorphology of rats liver can be impressed by Tripterygium Glycosides based on morphological and functional test,which is related with time.2.The activity of NK cell,T-cell and B-cell immune function were depressant effect by Tripterygium Glycosides too,and also concerned with the administration time.3.Tripterygium Glycosides lead to liver injury with the high secretion of TNF-α, from macrophage,high expression of Fas,and the accumulation of Ca²⁺ in the hepatocyte.4.Tripterygium Glycosides lead to apoptosis index of hepatocyte increased,and also concerned with the administration time.The periodicity ofhepatocyte apoptosis which mostly stayed at the stage of G₁(DNA presynthetic phase).5.The liver injury caused by Tripterygium Glycosides were recoverable at the certain time,and it depends on the intragastric administration time.