Study On The Recent Curative Effect In Active Rheumatoid Arthritis And Antifertility Action On Male Rats By Tong Bi 2 Composition

Rheumatoid arthritis(RA)is a systemic inflammatory autoimmune disease, with high rate of disability.Although the therapy strategy of RA has been studied extensively for many years,but the therapeutic outcome is not satisfied.Joint destruction occur in more than half patients.It is one of major diseases which cause loss of labor force and disability in China.Chinese medicine therapy on RA has distinct predominance,with definite curative effect,few by-effect,good tolerance and low expense.Prof.Ji-Fan CHEN make out one new composition named Tong Bi 2 Composition(TB2C)according to Tong Bi Ling Composition,which has wonderful curative effect for RA.It is made up of Tripterygium Hypoglaucum Hutch(THH)and Dipsacus Asperoides. Although clinical application of more than one decade indicate that this composition works well for RA,no systematic clinical research has ever been done about it.THH possess reproduction toxicity,when taken for a long time, it can result in menstrual disorder and male sterility.That's why its clinical application is confined.The clinical research was done to evaluate the curative effect for RA.And also,the experiment was done to approach antifertility effects of TB2C in male rats,and to investigate the sites,dose-effect relationship,reciprocity and possible mechanisms of the antifertility action.The researches help to provide clinical and experimental evidences for the treatment on RA by TB2C.1 Study on the Recent Curative Effect in Active RA by Tong Bi 2 CompositionThirty patients with active RA were treated with TB2C for 3 months. Clinical assessment using the American College of Rheumatology(ACR)criteria for improvement was performed at baseline and at the end of 3 months. Simultaneously the possible adverse reactions of TB2C were recorded,the clinical index including not only WBC,HGB,PLT,AST,ALT,Alb,BUN and CR in blood,but alsogastrointestinal tract indisposition,skin rash,skin damage,and women' s menstrual disorder,et al.The clinical result showed that after 3 months' treatment,the patients' swollen joint count and tender joint count decreased,morning stiffness time shortened,compared with that before treatment,showing statistical difference (P＜0.05),as well as the laboratory index such as ESR,CRP and RF tite(P＜0.05). In addition,there was remarkable improvement in disease activity following the TB2C treatment.At the end of 3 months,the percent age of ACR50 was 60 %(18/30).During the treatment period,no adverse reaction happened to liver function,kidney function,hemogram or gastrointestinal tract.Almost all the women patients got menstrual disorder after 3 months,such as delayed menorrhea,spanomenorrhea,and so on.In addition,hyperpigmentation,skiin rash and skin damage happened to some women patients.2 Resach on the Antifertility Action on Male Rats by Tong Bi 2 Composition90 male rats,weight 180～220g,were randomly divided into 5 groups, 18 in each group.The control group were given by gastric gavage filtering tap water at a dose of lOml·kg^-1·d^-1.In the same way the TB2C 1 group were given TB2C at a dose of 30g·kg^-1·d^-1,as well the TB2C 2 group at a dose of 10g·kg^-1·d^-1.The NST 1 group were given THH water elixation at a dose of 22.5g·kg^-1·d^-1,while the NST 2 group were given THH water elixation at a dose of 7.5g·kg^-1·d^-1.All rats were given by gastric gavage water or drug from the 1st day,once a day,last 60 days.Body weight was assessed every 5 days and the dose was adjusted accordingly.When administration 60d,one half the rats were sacrificed,and the corresponding index were measured,including testicle weight,testicle volume,the motility and counted number and density of sperm, pathological section of testicle and epididymis,the level of serum T,FSH, LH and E2,as well the level of WBC,HB,PLT,ALT,AST,Alb,BUN and Cr.When discontinuation 72d,the remnant half rats were sacrificed,and the above index were also measured in the same way.The findings showed,after administration 60d,no difference was seen in the TB2C 2 group compared with the control group,except that the motility of sperm from caudal epididymides dropped to zero.But after discontinuation 72d,the motility of sperm of the TB2C 2 group completed recovery.After administration 60d,a significant decrease in testicle weight,testicle volume, the counted number and density of sperm,were seen in the TB2C 1 group compared with the TB2C 2 group(P＜0.01).30g·kg^-1·d^-1of TB2C caused the damaged structures of testicle and epididymis,and after discontinuation 72d,the damaged structures didn't recover.And a significant decrease in testicle weight,testicle volume,the counted number and density of sperm,were seen in the NST 2 group compared with the TB2C 2 group(P＜0.01),while no difference was seen in the NST 1 group compared with the TB2C 1 group(P＞0.05).The findings also showed that no evident difference was seen on the level of FSH,LH and E2 between the 4 drug-given groups and the control group. Although a slight but statistically significant difference on the level of blood serum T was seen in the drug-given groups compared with the control group, which had no practical significance.Also no evident difference was seen on the level of FSH,LH and E2 between the 4 drug-given groups and the control group(P＞0.05).3 ConclusionTong Bi 2 Composition at the level of clinical frequently used dose (1g/kg/d)is effective and safe in patients with active RA.It can obviously affects women' menstruation,so it should be used carefully on young women. Tong Bi 2 Composition has a male antifertity effect in rats,testicle and epididymis are the target organ of the action.The antifertility action displays a dose-effect relationship.And the serum sexual hormone level did not show apparent changes,indicating that it may not play a significant role in TB2C-induced infertility.TB2C-induced infertility at dosage 10g/Kg/d foe 60 days in male rats possesses reciprocity.At a limited dosage level,Dipsacus Asperoides can rivalry the toxic action caused by THH in reproductive organ of male rats.Tong Bi 2 Composition at 10g/Kg/d and 30g/Kg/d dosages has no harmful effects on hemogram,liver and kidney function in male rats.