中华风湿病学杂志
中華風濕病學雜誌
중화풍습병학잡지
CHINESE JOURNAL OF RHEUMATOLOGY
2011年
11期
777-782
,共6页
魏华%许珂%侯广慧%赵文鹏%李小峰
魏華%許珂%侯廣慧%趙文鵬%李小峰
위화%허가%후엄혜%조문붕%리소봉
移植物抗宿主病%小鼠%长春新碱%环磷酰胺%治疗
移植物抗宿主病%小鼠%長春新堿%環燐酰胺%治療
이식물항숙주병%소서%장춘신감%배린선알%치료
Graft versus host disease%Mice%Vincristine%Cyclophosphamide%Therapy
目的 通过周期序贯联合免疫抑制剂(长春新碱、环磷酰胺)治疗慢性移植物抗宿主病(cGVHD)狼疮样小鼠肾脏病变的实验研究,以阐明序贯联合用药对小鼠肾脏病变的治疗效果显著,且不良反应较小.方法 选取cGVHD狼疮样小鼠模型30只,随机分为健康对照组、长春新碱间歇给药组、环磷酰胺隔日给药组、环磷酰胺间歇给药组、长春新碱+环磷酰胺联合间隔给药组.经18周治疗后观察并检测.采用单因素方差分析和重复测量的方差分析进行统计学处理.结果 ①诱导造模后6周尿蛋白定量(24 h)达(5.02±0.88) mg,抗双链DNA(dsDNA)抗体阳性,肾脏病理呈狼疮肾炎Ⅳ型表现,模型成功.②环磷酰胺隔日组[(0.48±0.32)mg ]、长春新碱+环磷酰胺联合组[(0.37±0.30)mg]对造模小鼠尿蛋白定量(24h)的改变最大,环磷酰胺间歇给药组、环磷酰胺隔日给药组与长春新碱+环磷酰胺联合给药组对造模小鼠尿单核细胞趋化蛋白(MCP)-1值、尿转化生长因子(TGF)-β1值的降低幅度较大；而不同给药方案对血清MCP-1、TGF-β1的改变差异无统计学意义(P＞0.05).环磷酰胺隔日给药组、长春新碱+环磷酰胺联合给药组造模小鼠肾脏MCP-1、TGF-β1表达在肾小球、肾小管中的阳性数最低,与对照组、长春新碱间歇给药组及环磷酰胺间歇给药组相比差异有统计学意义(P＜0.01).③长春新碱和环磷酰胺周期联合对造模小鼠血丙氨酸转氨酶、血肌酐、血抗dsDNA抗体、尿蛋白定量(24 h)、尿MCP-1、尿TGF-β1有交互作用(P＜0.05).结论 ①序贯周期联合长春新碱和环磷酰胺联合治疗有交互作用,在降低尿蛋白定量(24 h)、血清肌酐,减少肾脏MCP-1、TGF-β1的表达和排泌等方面有明显作用,与环磷酰胺隔日用药组相当,优于长春新碱间歇给药组、环磷酰胺间歇给药组.②长春新碱+环磷酰胺联合间歇给药与单用药比较不良反应并没有增加.环磷酰胺隔日给药组的不良反应明显大于其他各组,表现为体质量不增、肝酶增高.
目的 通過週期序貫聯閤免疫抑製劑(長春新堿、環燐酰胺)治療慢性移植物抗宿主病(cGVHD)狼瘡樣小鼠腎髒病變的實驗研究,以闡明序貫聯閤用藥對小鼠腎髒病變的治療效果顯著,且不良反應較小.方法 選取cGVHD狼瘡樣小鼠模型30隻,隨機分為健康對照組、長春新堿間歇給藥組、環燐酰胺隔日給藥組、環燐酰胺間歇給藥組、長春新堿+環燐酰胺聯閤間隔給藥組.經18週治療後觀察併檢測.採用單因素方差分析和重複測量的方差分析進行統計學處理.結果 ①誘導造模後6週尿蛋白定量(24 h)達(5.02±0.88) mg,抗雙鏈DNA(dsDNA)抗體暘性,腎髒病理呈狼瘡腎炎Ⅳ型錶現,模型成功.②環燐酰胺隔日組[(0.48±0.32)mg ]、長春新堿+環燐酰胺聯閤組[(0.37±0.30)mg]對造模小鼠尿蛋白定量(24h)的改變最大,環燐酰胺間歇給藥組、環燐酰胺隔日給藥組與長春新堿+環燐酰胺聯閤給藥組對造模小鼠尿單覈細胞趨化蛋白(MCP)-1值、尿轉化生長因子(TGF)-β1值的降低幅度較大；而不同給藥方案對血清MCP-1、TGF-β1的改變差異無統計學意義(P＞0.05).環燐酰胺隔日給藥組、長春新堿+環燐酰胺聯閤給藥組造模小鼠腎髒MCP-1、TGF-β1錶達在腎小毬、腎小管中的暘性數最低,與對照組、長春新堿間歇給藥組及環燐酰胺間歇給藥組相比差異有統計學意義(P＜0.01).③長春新堿和環燐酰胺週期聯閤對造模小鼠血丙氨痠轉氨酶、血肌酐、血抗dsDNA抗體、尿蛋白定量(24 h)、尿MCP-1、尿TGF-β1有交互作用(P＜0.05).結論 ①序貫週期聯閤長春新堿和環燐酰胺聯閤治療有交互作用,在降低尿蛋白定量(24 h)、血清肌酐,減少腎髒MCP-1、TGF-β1的錶達和排泌等方麵有明顯作用,與環燐酰胺隔日用藥組相噹,優于長春新堿間歇給藥組、環燐酰胺間歇給藥組.②長春新堿+環燐酰胺聯閤間歇給藥與單用藥比較不良反應併沒有增加.環燐酰胺隔日給藥組的不良反應明顯大于其他各組,錶現為體質量不增、肝酶增高.
목적 통과주기서관연합면역억제제(장춘신감、배린선알)치료만성이식물항숙주병(cGVHD)랑창양소서신장병변적실험연구,이천명서관연합용약대소서신장병변적치료효과현저,차불량반응교소.방법 선취cGVHD랑창양소서모형30지,수궤분위건강대조조、장춘신감간헐급약조、배린선알격일급약조、배린선알간헐급약조、장춘신감+배린선알연합간격급약조.경18주치료후관찰병검측.채용단인소방차분석화중복측량적방차분석진행통계학처리.결과 ①유도조모후6주뇨단백정량(24 h)체(5.02±0.88) mg,항쌍련DNA(dsDNA)항체양성,신장병리정랑창신염Ⅳ형표현,모형성공.②배린선알격일조[(0.48±0.32)mg ]、장춘신감+배린선알연합조[(0.37±0.30)mg]대조모소서뇨단백정량(24h)적개변최대,배린선알간헐급약조、배린선알격일급약조여장춘신감+배린선알연합급약조대조모소서뇨단핵세포추화단백(MCP)-1치、뇨전화생장인자(TGF)-β1치적강저폭도교대；이불동급약방안대혈청MCP-1、TGF-β1적개변차이무통계학의의(P＞0.05).배린선알격일급약조、장춘신감+배린선알연합급약조조모소서신장MCP-1、TGF-β1표체재신소구、신소관중적양성수최저,여대조조、장춘신감간헐급약조급배린선알간헐급약조상비차이유통계학의의(P＜0.01).③장춘신감화배린선알주기연합대조모소서혈병안산전안매、혈기항、혈항dsDNA항체、뇨단백정량(24 h)、뇨MCP-1、뇨TGF-β1유교호작용(P＜0.05).결론 ①서관주기연합장춘신감화배린선알연합치료유교호작용,재강저뇨단백정량(24 h)、혈청기항,감소신장MCP-1、TGF-β1적표체화배비등방면유명현작용,여배린선알격일용약조상당,우우장춘신감간헐급약조、배린선알간헐급약조.②장춘신감+배린선알연합간헐급약여단용약비교불량반응병몰유증가.배린선알격일급약조적불량반응명현대우기타각조,표현위체질량불증、간매증고.
Objective To 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.Methods Murine 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.Results ① 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 VCR and CTX combination treatment was effective in 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.
