Effect and mechanisms of combined immunosuppressive agents sequential therapy in murine models of chronic graft-versus-host disease
10.3760/cma.j.issn.1007-7480.2011.11.013
- VernacularTitle:长春新碱和环磷酰胺周期序贯联合对慢性移植物抗宿主病狼疮样小鼠肾脏病变的疗效研究
- Author:
Hua WEI
;
Ke XU
;
Guanghui HOU
;
Wenpeng ZHAO
;
Xiaofeng LI
- Publication Type:Journal Article
- Keywords:
Graft versus host disease;
Mice;
Vincristine;
Cyclophosphamide;
Therapy
- From:
Chinese Journal of Rheumatology
2011;15(11):777-782
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the effects and possible mechanisms of VCR combined with low dose cyclophosphamide(CTX) intermittently to treat severe systemic lupus erythematosus(SLE).It is assumed that this might be a new combination therapy for SLE and expected to improve the overall prognosis and outcome of SLE.MethodsMurine chronic graft-versus-host disease(cGVHD) model were developed for study.They were randomly divided into the control group,vincristine (VCR) pulse therapy group,CTX pulse therapy group,CTX every other day(EOD) group,VCR+CTX combination group.One way ANOVA and repeated measure variance analysis were used for statistical analysis.Results① Six weeks after cGVHD models were set up,the average 24-hour urine protein quantification was(5.02±0.88) mg,anti-dsDNA antibody was positive,and Ⅳ LN pathology could be observed histologically in the model murine.So cGVHD models were successfully developed.② Significantly difference in decreasing of 24-hour urine protein quantification was found in the CTX EOD group,VCR+CTX combination group and other groups (P＜0.01).Significant decrease in Cr,ALT,anti-dsDNA,was found in the CTX EOD group,VCR+CTX combination group,CTX pulse therapy group and other groups(P＜0.05).Decrease in urine MCP-1 and TGF-β1 could be detected,and statistical significant difference in these parameters could be found in the CTX EOD group,CTX pulse therapy group,VCR+CTX combination group and other groups (P＜0.01).MCP-1 and TGF-β1'expression in model kidney were reduced in the CTX EOD group,VCR+CTX combination group and had statistical significant difference in the CTX EOD group,VCR+CTX combination group,VCR pulse therapy group,and CTX pulse therapy group.③ VCRand CTX combination treatment was effectivein 24-hour urine protein quantification,blood Cr,ALT,anti-dsDNA and urine MCP-1,as well as urine TGF-β1 (P＜0.05).Conclusion ① The combination of VCR and CTX is synergistic in decreasing 24-hour urine protein quantification,Cr,and the expression of MCP-1,TGF-β1.② The adverse effect of VCR+CTX combination group is similar to VCR pulse therapy group and CTX pulse therapy group.
