The Protective Effect Of Xiaoyao San To The Renal Toxicity Models Of Renal Toxicity In Rats Induced By Tripterygium Wilfordii

Objective:By using different doses of water decoction of Tripterygium wilfordii(15g·kg^-1,30g·kg^-1,60g·kg^-1)in this experiment,we establish the renal toxicity models of rats in order to find the optimal dose and time of drug administration.And to explore the protective effect of Xiaoyao San to the models of rats with renal toxicity induced by Tripterygium wilfordii.By making use of the traditional Chinese medicine prescription to resist the renal toxicity of Tripterygium wilfordii,the advantages of traditional Chinese medicine in the aspect of reducing the toxicity of Tripterygium wilfordii will be brought into play adequately.Methods:1.The first part:Establishment of the renal toxicity model of rats induced by Tripterygium wilfordii:There were 40 SD rats,male and female half-and-half.After a week of adaptive feeding,the rats were randomly divided into 4 groups,10 rats in each group:normal control group?NC?,low dose TW group?TWLD?,middle dose TW group?TWMD?,High dose TW group?TWHD?.The specific method of making model is:the rats of TWLD,TWMD and TWHD groupwerefedwith Tripterygiumwilfordii solution(15g·kg^-1,30g·kg^-1,60g·kg^-1).NC group was given equal volume of saline according to the weight for 1 time a day,and the continuous medication was for 60 days.At the time of10-days,20-days,30-days,40-days,50-days and 60-days,all the rats were treated with the water decoction of Tripterygium wilfordii.After 6 hours,we would collect blood from orbital venous plexus to measure the consentration of blood urea nitrogen?BUN?and serum creatinine?SCR?.All rats were given Tripterygium wilfordii Decoction after 8 hours,collecting 24-hours urine of rats by using metabolic cage to determinate the contant of24-hours urinary protein?24hUP?.At the time of 62-days of the experiment,we removed the kidney of rats and calculated the organ coefficient.And than we fixed the kidney in 10%Formaldehyde Solution,established the sections and made HE staining to observe the pathological changes under the light microscope.2.The second part:The protective effect of Xiaoyao San to the renal toxicitymodels of rats induced by Tripterygium wilfordii:There were 50 SD rats,male and female half-and-half,After a week of adaptive feeding,the rats were randomly divided into 5groups,10 rats in each group:blank control group?NC?,model TW group?TWM?,low dosage XYS group?XYSL?,middle dosage XYS group?XYSM?and high dosage XYS group?XYSH?.TWM group was given Tripterygium wilfordii solution(30g·kg^-1)in the morning and equal volume of saline in the afternoon;XYSL,XYSM and XYSH groups were given Tripterygium wilfordii solution(30g·kg^-1)in the morning and Xiaoyao San solution(3.375g·kg^-1,6.75g·kg^-1,13.5g·kg^-1)respectively in the afternoon;NC group was given equal volume of saline according to weight in the morning and afternoon.All the rats were given Tripterygium wilfordii solution or equal volume of saline by gavage for 60 days.After 8 hours of all the rats given the final drug administration,we would collect urine of rats in 24-hours by using metabolic cage to determinate the contant of 24-hours urinary protein?24hUP?.On 62-days of the experiment,all the rats were collected blood from abdominal aorta in anesthesia to measure the consentration of blood urea nitrogen?BUN?and serum creatinine?SCR?;and than removed the kidney and calculated the organ coefficient.The left kidneys were fixed in 10%Formaldehyde Solution,established section and made HE staining to observe the renal tissue pathological changes under the light microscope;the right kidneys were in a homogenate to measure the activity of superoxide dismutas?SOD?and glutathione peroxidase?GSH-Px?,and the content of maleic dialdehyde?MDA?.Results:1.The first part:Establishment of the renal toxicity model of rats induced by Tripterygium wilfordii:Compared with NC group,the consentration of BUN and SCR in TWM group and TWH group increased significantly?P<0.05,P<0.01?;the content of24hUP in TWLD group,TWMD group and TWHD group increased significantly?P<0.05,P<0.01?;the renal coefficient of TWMD and TWHD group was significantly reduced?P<0.05,P<0.01?.The renal histopathological examination results showed that both TWMD group and TWHD group arose the atrophic glomerulus;the regenerated renal papillae and renal tubule,protein casts and red blood cells,some epithelial cells of renal tubule in renal cortexwere hypertrophic and hyperplastic,a little inflammatory cells infiltrated in mesenchyma.2.The second part:The protective effect of Xiaoyao San to the renal toxicity models of rats induced by Tripterygium wilfordii:Compared with TWM group,the consentration of BUN,SCR and the content of 24hUP of different doses of XYS antagonism groups decreased without exception?P<0.05,P<0.01?,of which the XYSM group and XYSH group's antagonism effects were obvious.Compared with TWM group,The activity of SOD and GSH-Px of different doses of XYS antagonism groups increased without exception,and the contant of MDA decreased significantly?P<0.05,P<0.01?.Compared with NCgroup,kidneyorgancoefficientofTWMgroupdecreasedsignificantly?P<0.01?;Different doses of XYS antagonism groups showed the up trend but without statisticalsignificances;comparedwithTWMgroup,XYSHgroupdecreased significantly?P<0.01?.The renal histopathological examination results showed that TWM group arose the atrophic glomerulus;the protein casts in renal papillae and renal tubule,inflammatory cells infiltrated in partial mesenchyma.Different doses of XYS antagonism groups improved significantly.Conclusion:1.The middle dose of Tripterygium wilfordii(30g·kg^-1)intervention for 60 days can be used as the optimal dose and time of grug administration to establish the renal toxicity models of rats induced by Tripterygium wilfordii.2.Different doses of Xiaoyao San have protective effects to the renal toxicity models of rats induced by Tripterygium wilfordii.But XYSM group and XYSH group have more protective effects than XYSL group.3.Different doses of Xiaoyao San can significantly improve the antioxidant ability of the renal toxicity model of rats induced by Tripterygium wilfordii,there are no significant difference among different doses of XYS antagonism groups.