中华风湿病学杂志
中華風濕病學雜誌
중화풍습병학잡지
CHINESE JOURNAL OF RHEUMATOLOGY
2012年
3期
177-181
,共5页
王红%谢奇朋%孙莉%朱小春
王紅%謝奇朋%孫莉%硃小春
왕홍%사기붕%손리%주소춘
狼疮%甲基转移酶类%抗原,CD11a%抗dsDNA抗体%砷剂
狼瘡%甲基轉移酶類%抗原,CD11a%抗dsDNA抗體%砷劑
랑창%갑기전이매류%항원,CD11a%항dsDNA항체%신제
Lupus%Methyltransferases%Antigens,CD11a%Anti-dsDNA antibody%Arsenicds
目的 探讨三氧化二砷(ATO)对MRL/lpr自发性狼疮小鼠抗双链DNA(dsDNA)抗体及DNA甲基转移酶1(DNMT1)和黏附分子淋巴细胞功能相关抗原-1(LFA-1)的亚基CD11a表达的影响及其可能作用机制.方法 将MRL/lpr狼疮鼠随机分为ATO治疗组、0.9％氯化钠注射液(NS)对照组和环磷酰胺组.另设正常C57/BL小鼠,随机分为ATO治疗组和NS对照组.以上每组各10只,隔日腹腔注射,给药2个月后处死,SYSMEX KX21血常规测定仪测定血常规,酶联免疫吸附试验(EMSA)法测各组小鼠血清抗dsDNA抗体水平；反转录.聚合酶链反应(RT-PCR)检测2组小鼠外周血单个核细胞的DNMT1及CD11a转录水平的表达情况.采用方差分析和配对t检验进行统计学处理.结果 ①MRL/lpr小鼠ATO 治疗组血清抗dsDNA抗体水平(0.89±0.07)和CD11 a(0.43±0.25)均低于NS对照组(1.77±0.28.P＜0.01和0.99±0.31,P＜0.05),DNMT1 (0.32±0.30)高于NS对照组(0.16±0.26,P＜0.05)；②MRL/lpr小鼠ATO治疗组及环磷酰胺治疗组小鼠的血清抗dsDNA抗体水平(分别为0.90±0.07和0.66±0.22)较NS组(1.77±0.28)下降,且ATO治疗组小鼠的血清抗dsDNA抗体水平高于环磷酰胺治疗组(P＜0.05):ATO组DNMT1(0.32±0.30)高于环磷酰胺治疗组(0.16±0.18,P＜0.05),CD11 a(0.43±0.25)低于环磷酰胺治疗组(0.86±0.31,P＜0.05)；③在C57/BL小鼠中.ATO治疗组和NS对照组之间以上指标差异均无统计学意义.结论 ATO 能减少狼疮小鼠体内自身抗体产生,逆转其低甲基化状态；但是对正常小鼠的抗体水平和其甲基化状态并无明显影响.
目的 探討三氧化二砷(ATO)對MRL/lpr自髮性狼瘡小鼠抗雙鏈DNA(dsDNA)抗體及DNA甲基轉移酶1(DNMT1)和黏附分子淋巴細胞功能相關抗原-1(LFA-1)的亞基CD11a錶達的影響及其可能作用機製.方法 將MRL/lpr狼瘡鼠隨機分為ATO治療組、0.9％氯化鈉註射液(NS)對照組和環燐酰胺組.另設正常C57/BL小鼠,隨機分為ATO治療組和NS對照組.以上每組各10隻,隔日腹腔註射,給藥2箇月後處死,SYSMEX KX21血常規測定儀測定血常規,酶聯免疫吸附試驗(EMSA)法測各組小鼠血清抗dsDNA抗體水平；反轉錄.聚閤酶鏈反應(RT-PCR)檢測2組小鼠外週血單箇覈細胞的DNMT1及CD11a轉錄水平的錶達情況.採用方差分析和配對t檢驗進行統計學處理.結果 ①MRL/lpr小鼠ATO 治療組血清抗dsDNA抗體水平(0.89±0.07)和CD11 a(0.43±0.25)均低于NS對照組(1.77±0.28.P＜0.01和0.99±0.31,P＜0.05),DNMT1 (0.32±0.30)高于NS對照組(0.16±0.26,P＜0.05)；②MRL/lpr小鼠ATO治療組及環燐酰胺治療組小鼠的血清抗dsDNA抗體水平(分彆為0.90±0.07和0.66±0.22)較NS組(1.77±0.28)下降,且ATO治療組小鼠的血清抗dsDNA抗體水平高于環燐酰胺治療組(P＜0.05):ATO組DNMT1(0.32±0.30)高于環燐酰胺治療組(0.16±0.18,P＜0.05),CD11 a(0.43±0.25)低于環燐酰胺治療組(0.86±0.31,P＜0.05)；③在C57/BL小鼠中.ATO治療組和NS對照組之間以上指標差異均無統計學意義.結論 ATO 能減少狼瘡小鼠體內自身抗體產生,逆轉其低甲基化狀態；但是對正常小鼠的抗體水平和其甲基化狀態併無明顯影響.
목적 탐토삼양화이신(ATO)대MRL/lpr자발성랑창소서항쌍련DNA(dsDNA)항체급DNA갑기전이매1(DNMT1)화점부분자림파세포공능상관항원-1(LFA-1)적아기CD11a표체적영향급기가능작용궤제.방법 장MRL/lpr랑창서수궤분위ATO치료조、0.9％록화납주사액(NS)대조조화배린선알조.령설정상C57/BL소서,수궤분위ATO치료조화NS대조조.이상매조각10지,격일복강주사,급약2개월후처사,SYSMEX KX21혈상규측정의측정혈상규,매련면역흡부시험(EMSA)법측각조소서혈청항dsDNA항체수평；반전록.취합매련반응(RT-PCR)검측2조소서외주혈단개핵세포적DNMT1급CD11a전록수평적표체정황.채용방차분석화배대t검험진행통계학처리.결과 ①MRL/lpr소서ATO 치료조혈청항dsDNA항체수평(0.89±0.07)화CD11 a(0.43±0.25)균저우NS대조조(1.77±0.28.P＜0.01화0.99±0.31,P＜0.05),DNMT1 (0.32±0.30)고우NS대조조(0.16±0.26,P＜0.05)；②MRL/lpr소서ATO치료조급배린선알치료조소서적혈청항dsDNA항체수평(분별위0.90±0.07화0.66±0.22)교NS조(1.77±0.28)하강,차ATO치료조소서적혈청항dsDNA항체수평고우배린선알치료조(P＜0.05):ATO조DNMT1(0.32±0.30)고우배린선알치료조(0.16±0.18,P＜0.05),CD11 a(0.43±0.25)저우배린선알치료조(0.86±0.31,P＜0.05)；③재C57/BL소서중.ATO치료조화NS대조조지간이상지표차이균무통계학의의.결론 ATO 능감소랑창소서체내자신항체산생,역전기저갑기화상태；단시대정상소서적항체수평화기갑기화상태병무명현영향.
Objective To investigate the effect of arsenic trioxide (ATO) on anti-dsDNA antibody and the expression of DNA methyltransferase 1-mRNA and CD11a-mRNA in lupus MRL/lpr mice.Methods MRL/lpr mice were divided into three groups:the ATO group,the sodium chloride (NS) group,and the cyclophosphamide (CTX) group.The control group consisted of 20 syngeneic normal C57/BL mice,which were subdivided into the ATO group and the NS group.After two-month treatment,all mice were sacrificed.Blood routine test was conducted by SYSMEX KX21.The anti-dsDNA antibody in the serum were detected by ELISA.The expression of DNMT1 and CD11a was determined by RT-PCR.ANOVA and paired t test were used for statistical analysis.Results ① The serum level of anti-dsDNA antibody (0.89±0.07) and the gray scale value of CD11a-mRNA (0.43±0.25) in the ATO group were much lower than those in the NS group of MRL/lpr mice (1.77±0.28,P＜0.01; 0.99±0.31,P＜0.05),while the gray scale value of DNMTI-mRNA (0.32±0.30) was significantly higher than that in the NS group (0.16±0.26,P＜0.05 ).② The serum levels of anti-dsDNA antibody was low in both the ATO group and the CTX group (0.90±0.07,0.66±0.22),and it was higher in the ATO group than that in the CTX group (P＜0.05).The gray scale value of DNMT1 mRNA in the ATO group (0.32±0.30) was higher than that in the CTX group (0.16±0.18,P＜0.05) in MRL/lpr mice,and the gray scale value of CD11a mRNA in the ATO group (0.43±0.25) was lower than that in the CTX group (0.86±0.31,P＜0.05) in MRL/lpr mice.③ There was no difference in above parameters between the ATO-group and NS group in C57/BL mice (P＞0.05).Conclusion Arsenic trioxide can reduce the serum level of auto-antibody and reverse low methylation.But it has no effect on normal mice.
