Experimental Study Of The Mechanism Of The Liver And Kidney Toxicity And Immunotoxicity Of Tripterygium Glycosides

Tripterygium wilfordii glucosides is one of the common anti-rheumatism medicine in our market,its clinical application is unique and therefore emphasized at home and abroad. On the other hand,its side effects have become gradually gotten attention.And,the immunological effects of Tripterygium wilfordii glucosides are can be considered as a immunological poisonous effect.This study aims to:1.explore the immunological effects of Tripterygium wilfordii glucosides,examining the apoptosis mechanism caused by Tripterygium wilfordii glucosides.2.verify the common mechanism between the immunological and poisonous effects of Tripterygium wilfordii glucosides,providing experimental evidence for its rational clinical application.After looking for literature and related materials,the study chooses SD rats as experimental objects,which were divided into 8 groups,normal reference groups,low, medium and high doses groups and so on.Three weeks after the rats were administered,the study first check the immune organ index,cell immunology and body fluid immunological function.There are much reports about the poisonous effects of the Tripterygium wilfordii glucosides on the liver,kidney,and reproductive organs,which are the important proliferation and metabolic organs.Hence we choose liver and kidney as the study objects, exploring whether there its damage is related to the immunological poison of Tripterygium wilfordii glucosides on the basis of the normal function and indices of liver and kidney.The results show,vs control group,the indexes of spleen,activity of NK cell and T,B tymphocyte of low dose group had no significant changes;the indexes of spleen and thymus, activity of NK cell and T,Blymphocyte of medium dose group decreased significantly;the indexes of spleen and thymus,activity of NK cell and T,B lymphocyte of high dose group decreased significantly.And two weeks later,the index of thymus did not recovery.The objects of study are liver and kidney.Experiment results show an obvious rise on mice serum for ALT,AST,ALP,BUN and Cr,so do for liver and kidney indices,which is of statistical meaning contrasted with normal reference group(P＜0.05),especially for high dose group(P＜0.01).Two weeks after stopping administration,the indicators in medium-dose group can turn normal(P＜0.05),and it's not so for high-dose group.Then we use immunohistochemical method to examine CD₆₈⁺,CD₆₀,Fas,TNF-α,and so on.The results indicate an increase in CD₆₈⁺ and CD₄₀(P＜0.05),and so is for Fas(P＜0.05) and TNF-α(P＜0.05);liver apoptosis(P＜0.05),particularly for medium- and high doses groups.Lastly,the study use pathological slice to qualitatively analyze the change in the cell form of liver and kidney.Pathological organization observes different reaction for low, medium and high dose groups.Two weeks after the stopping of administration,the medium dose group can turn normal,but there is no recovery for the injuries in liver and kidney of high dose group.The above research results show the suppressive effects by tripterygium wilfordii glucosides on some of the immunological functions,with certain time-effect relationship. But as an external chemical medicine,tripterygium wilfordii glucosides cause injuries on the partial immunology of mouse liver and kidney,which is positively related to dosage. However,the injury for the medium- and low dose group are reversible two weeks after the end of administration.The possible immunological injury mechanism is as follows:some ingredients of tripterygium wilfordii glucosides transform to electrophilic group or free radical,and covalentty combine with macromolecular substances or cause lipid peroxidation to make liver and kidney cells necrosis.The necrotic cetts can activate the macrophages to excrete a large amount of TNF-αand make the expression of Fas in liver and kidney increase to aggravate the injury of liver and kidney.The necrotic cells can also make lymphocytes and inflammatory cells migrate to injured area to start a series of immunologic injuries.