| Background Tripterygium as traditional Chinese medicine in china,the existingblindly 700 years of history,with promoting blood circulation to remove blood stasis,qingrejiedu, detumescence insecticidal,improving the effect such as bleeding.Tripterygium is very extensive in modern medicine,pharmacology and clinical research comfirmed,Tripterygium have Anti-inflammatory,antitumor,immunoregulation,antifertility and so on, involve endocrine system,respiratory system,dermatologist,ophthalmology,gynecology and other areas.In recent years clinical widely used to treat rheumatoid arthritis,chronic nephritis,uterine fibroids,organ and other diseases.But it was production toxicity for digestion,reproductive,urinary,blood system while it show effect,much limitde its application.This is mainly because of tripterygium complicated ingredients,contain a variety of alkaloids,terpenoids and nucleoside composition.Some of these elements is effective component and toxic ingredients.Therefore,how to overcome tripterygium toxic,developed more low-toxic and effective tripterygium preparation have broad development prospects.Research shows that, tripterygium have toxic for reproductive, urinary,blood system.But to the heart only in clinical case has toxic reports, the pre-clinical heart toxicity studies too less.Serum pharmaceutical chemistry based on traditional medicinal chemistry variety of modern technology,comprehensive application from serum isolation,identification transitions composition,research serum transitions composition and the correlation of traditional curative effect,determine efficacy material base applying subject. Serum pharmaceutical chemistry based on traditional medicinal chemistry variety of modern technology,comprehensive application from serum isolation,identification transitions composition,research serum transitions composition and the correlation of traditional curative effect,determine efficacy material base applying subject,This study is the first to adopt serum drug chemical research methods,mainly in into the blood analysis of tripterygium ingredients,combined with the animal experiment results,which were for preliminary produce toxic effect in the heart of active ingredients to lay the foundation.Objectives Research the effects of Trptergium extract on toxic of rats heart,combined with High performance liquid chromatography process analysis of serum pharmaceutical chemistry.Methods Serum pharmaceutical chemistry:First,established a HPLC method,that can be used to determine tripterygium extract of serum pharmaceutical chemistry.And ensure the stability and precision,recovery make experiment results are reliable.Rats abrosia 12h ,free water before experiment,irrigates the stomach 10mg·mL-1 of tripterygium extract 1mL·100g-1.Respectively on give medivine before and after 0.5,1,2,4,8,12,16,24h.Intubation the blood by femoral artery,preparation of serum.Using HPLC to determine respectively fingerprints of tripterygium extract.Heart toxicity testing:Pre-register experiment,be sure to give doses.In this randomized,the experimental rats were divided into four groups,including tripterygium extract low doses group,tripterygium extract middle group ,tripterygium extract high doses group and control group .Control group were irritates the stomach to physiological saline,the other each group were irritates the stomach to different concentrations of tripterygium extract solution.Acute toxicity experience to medicine once,long-term toxicity was give medicine once daily,continuous 90d.Record each rats weight,testing the electrocardiogram,serum potassium and heart function in pre-administration and after administration on different time points.The pathology changes were evaluated by Haematoxylin-eosin(HE).The database was established with Excel,the obtained data were represented as mean±SD,and the analysis was carried on with SPSS15.0,each group potassium and electrovardiogram compares the matching t-test,each group cardiac function compares the monitoring indicators of bilateral t-test.Results Serum pharmacochemistry:Tripterygium extract was well separated under this method and there was no significant interferential pdak,8 components appeared successively in serum in 24 hours after adminiatration,five of them were original comotents contained in Tripterygium extract,two of them were metabolites,one of them was a permanent component of serum.One of 8 components was identified as triptolide.Each component into blood has different time,but has elevated concentrations forst and than decline trend.Acute toxicity: Compared with the control group and pre-administration, the low dose potassium decreased significantly,on the 4-8h.On the 24h,the potassium devreased signifivantly of after administrated compared with the control group(P<0.05).The potassium of middle dose group devreased signifivantly after administrated 2-24h,than the potassium devreased compared with the control group(P<0.05),there were no changes significantly compared with pre-administration(P>0.05) . The potassium devreased of the high dose group after administrated 2-4h(P<0.05),the potassium devreased signifivantly on 8-24h(P<0.01).Compared with pre-administrated and the control group, QT interval, QRS interval ,ST interval,ST segment and heart rate of low dose group was changes after administrated 4-12h(P<0.05). QT interval, QRS interval ,ST interval,ST segment and heart rate of middle dose group was changes signifivantly on 2-24h(P<0.05 or P<0.01).Over each index of high dose group from 1h to 24h was changes signifivantly(P<0.05 or P<0.01).Compared with the control group, LVSP of low dose group after administrated on 2-8h, the middle dose group and the high dose group on 2-12h were devreased signifivantly(P<0.05 or 0.01).LVEDP of all dose groups after administrated were increased significantly on 2-12h. +dP/dtmax was invreased significantly of low dose group from 2-24h, the middle group and the high dose group from 2-12h(P<0.05 or 0.01). -dp/dtmax was invreased significantly of low dose group from 4-8h,the middle dose group and the high dose group from 2-8h(P<0.05或0.01).The myocardial fiber was arrangement rules of control group and low dose group ,the myocardial membrane completed,the myocardial cell nuclear membrane and chromatin clear, there wew parts of Myocardial cell fractured of middle dose group,and there were inflammatory cells infiltration of high dose group.The long-term toxicity:Compared with the control group and pre-administration,the potassium of low dose group was no changes(P>0.05).The potassium of middle dose group after adminsitrated was devreased on 90d (P<0.05).On 30-90d, the potassium of high dose group after adminsitrated was devreased significantly (P<0.01).Compared with the control group and pre-administration,QT interval, QRS interval ,ST segment and heart rate were no changes except ST interval, it was prolonged on 60d after administration(P<0.05).QT interval, QRS interval,ST segment were prolonged on 60d of middle dose group after administration(P<0.05),the heart rate was decreased and ST segment prolonged(P<0.05).ST segment and QRS interval were prolonged on 15d of high dose group after administration(P<0.05), the QT interval was prolonged,heart rate and ST segment were devreased of after administration on 15d(P<0.05).Compared with the control group, LVSP was no changes of low dose group in each time poin(tP>0.05),on 60d and 15d LVSP were decreased of middle dose group and high dose group after administration(P<0.05).LVEDP was no changes of low dose group, LVEDP were increased respectively on 90d and 30d of middle dose group and high dose group after administration(P<0.05).±dp/dtmax were no changes of low dose after administration(P>0.05),±dp/dtmax were invreased respectively on 60d and 30d of middle dose group and high dose group after administration(P<0.05).HE respectively visible:The control group myocardial fiber was arrangement rules, the myocardial membrane completed,the myocardial cell nuclear membrane and chromatin clear.The low dose group myocardial fiber was arrangement rules,the myocardial membrane completed . The middle dose group myocardial fiber fuzzy,fractured,cell nuclear atrophy. The high dose group myocardial cells ruptured,vacuolar degeneration,cytoplasm abscurde, cell nuclear death.Conclusions: Tripterygium extract of serum pharmacochemistry could preliminary ascertainment the metabolism composition or prototype composition in serum .Tripterygium extract has acute toxicity to rats heart, could decreased serum potassium, there were changes electrocardiogram and heart function of rats. It no significantly on myocardium.Tripterygium extract long-term prescription has toxicity for rats heart, the serum potassium decreased significantly, there were changes electrocardiogram and heart function of rats,it was changes significantly on myocardium for rats heart. |
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