摘要
目的观察长春新碱序贯环磷酰胺治疗对狼疮肾炎患者外周血单个核细胞(PBMC)B淋巴细胞活化因子(BAFF)的影响,为序贯治疗提供理论依据。方法狼疮肾炎患者20例,随机分入激素+环磷酰胺组(传统组,n=10,环磷酰胺600～800mg,静脉滴注,每3周1次)和激素+长春新碱+环磷酰胺组(序贯组,n=10,长春新碱1mg静脉滴注后24小时再滴注环磷酰胺400mg,每3周1次),两组患者均同时口服泼尼松1mg/kg。共治疗24周。另选10例健康志愿者作为正常对照组。各组治疗前后常规行狼疮疾病活动性计分(SLEDAI)评估,检测尿蛋白定量、补体C3、丙氨酸转氨酶(ALT)、抗双链DNA抗体浓度(抗ds-DNA)、血常规等指标,并留静脉血提取单个核细胞(PBMC)应用蛋白质印迹(western blot)和反转录聚合酶链反应(RT-PCR)方法检测BAFF蛋白及mRNA的表达。结果传统组和序贯组患者治疗前SLEDAI、尿蛋白、抗ds-DNA、BAFF蛋白及mRNA表达均较正常对照组升高;SLEDAI(17.2±5.2)分、(18.4±5.4)分vs(0.1±0.1)分;尿蛋白(4.01±1.870)g/d、(3.94±1.73)g/d vs(0.11±0.01)g/d;抗ds-DNA(2.27±0.61)OD、(2.55±0.48)OD vs(0.25±0.09)OD;BAFF蛋白0.28±0.04,0.27±0.04vs 0.08±0.01;BAFF-mRNA 0.23±0.04、0.22±0.02vs 0.07±0.01(均P<0.01),而补体C3较正常对照下降(0.65±0.22)g/L、(0.61±0.26)g/L vs(1.45±0.21)g/L(P<0.05)。与传统组比较,治疗后序贯组SLEDAI、BAFF蛋白及mRNA、抗ds-DNA、24小时尿蛋白定量下降更明显(P<0.01),C3上升更明显(P<0.05)。ALT及外周血白细胞计数差异无统计学意义(P>0.05),两治疗组间不良反应差异无统计学意义。结论长春新碱序贯环磷酰胺治疗狼疮肾炎能使BAFF在PBMC的表达明显下降,抗免疫紊乱效果优于单用环磷酰胺,且两者联用不良反应无明显增加。
Objective To explore the clinic efficacy of sequential immunosuppressive regimen,vineristine（VCR） followed by cyclophosphamide（CTX） ,on B lymphocyte activating factor（BAFF） in patients with lupus nephritis（LN）. Methods Twenty new-onset LN patients meeting the criteria of systemic lupus erythematosus were randomly divided into two groups..CTX group and VCR＋ CTX group, 10 patients in each group. Ten healthy volunteers served as normal controls. The patients in CTX group were given CTX 600-800 mg intravenously every three weeks;those in VCR＋CTX group were given CTX 400. mg intravenously after 24 hours of being given VCR（1 mg） every three weeks, too. Orally prednisone 1 mg/kg was administered in both treatment groups. The duration was totally 24 weeks. Before and after the treatment, the systemic lupus erythematosus disease activity index（SLEDAI） was evaluated, urine protein was detected, complement 3, alanine aminotransferase （ ALT）, anti-double-strand DNA （ anti-ds-DNA）, blood routine and others were determined. The peripheral blood mononuclear cells （PBMC） were separated to determine the expression of BAFF protein and message RNA with western blot and RT-PCR. Results Compared with those in healthy group before treatment, SLEDAI, urine protein, anti-ds-DNA, BAFF protein and mRNA in CTX group and VCR＋ CTX group all increased signifieantly,SLEDAI（17.2±5.2） marks, （18.4±5.4） marks vs （0.1±0.1） marks urine protein（4.01±1. 870） g/d,（3.94±1.73） g/d vs （0.11±0.01） g/d;anti-ds-DNA （2.27±0.61） OD,（2.55±0.48） OD vs （0.25±0.09） OD;BAFF protein 0.28±0.04,0.27±0.04 vs 0. 08±0.01,BAFF-mRNA 0. 23±0.04,0.22±0.02 vs 0.07± 0.01（all P 〈0.01） ,while complement 3 in the two treatment groups decreased significantly, （0.65±0. 22） g/L, （0. 61 ±0.26） g/L vs （1.45±0.21） g/L（ P 〈0.05）. SLEDAI,expression of BAFF protein and message mRNA,anti-ds-DNA and urine protein were significantly lower in sequential treatment group （ P 〈 0.01 ）, complement 3 increased more compared with those in CTX group（ P d0. 05）, but there were no significant difference in ALT and leucocyte count（ P 0.05）. There were no more adverse effect aroused by VCR＋CTX group than by CTX alone treatment. Conclusion Sequential therapy can attenuate immunologic disorders via decreasing the expression of BAFF in PBMC in patients with LN.
出处
《临床荟萃》
CAS
2012年第11期933-936,共4页
Clinical Focus
基金
河北省科技厅资助项目(10276105D-68)
邯郸市科技局资助项目(1023108102)
关键词
狼疮肾炎
B细胞活化因子
长春新碱
环磷酰胺
lupus nephritis B lymphocyte activating factor vincristine cyclophophamide
