中华风湿病学杂志
中華風濕病學雜誌
중화풍습병학잡지
CHINESE JOURNAL OF RHEUMATOLOGY
2011年
12期
843-845
,共3页
胡军林%欧阳桂林%高华利%李宁丽%黄志明%黄正%解骏%沈佰华%王利%肖涟波
鬍軍林%歐暘桂林%高華利%李寧麗%黃誌明%黃正%解駿%瀋佰華%王利%肖漣波
호군림%구양계림%고화리%리저려%황지명%황정%해준%침백화%왕리%초련파
关节炎,实验性%甲氨蝶呤%骨破坏
關節炎,實驗性%甲氨蝶呤%骨破壞
관절염,실험성%갑안접령%골파배
Arthritis,Experimental%Methotrexate%Bone destruction
目的 通过建立胶原诱导性关节炎(CIA)大鼠模型,评价单用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc)及其联合甲氨蝶呤在抑制CIA大鼠关节骨破坏方面的作用及机制.方法 利用皮下注射牛Ⅱ型胶原诱导Wistar大鼠发病,建立CIA大鼠模型.将造模成功,炎症评分≥2分的CIA大鼠随机分为生理盐水组(0.4 ml/周,腹腔注射)、甲氨蝶呤治疗组(1 mg周,腹腔注射)、rhTN FR:Fc治疗组(0.8 mg,每周2次,腹腔注射)、甲氨蝶呤+rhTN FR:Fc治疗组(甲氨蝶呤1 mg/周+rhTNFR:Fc 0.8mg,每周2次,腹腔注射).治疗8周后,处死大鼠,取踝关节拍摄X线片,胫骨上段行微计算机断层扫描技术扫描和制作硬组织切片,观察各组踝关节骨破坏情况,评价胫骨上段骨小梁变化及骨量变化.统计学处理采用SNK-q检验.结果 治疗8周后,rhTN FR:Fc组,甲氨蝶呤+rhTNFR:Fc组骨小梁面积百分数[(29.1±0.3)％,(26.7±0.6)％]及骨小梁数量(4.4±0.5)/mm,( 4.0±0.6 )/mm]明显高于0.9％氯化钠注射液组和甲氨蝶呤组[(12.9±0.5)％,( 13.2±0.4)％与(2.0±0.3 )/mm,(2.2±0.2)/mm](P＜0.01)；rhTNFR:Fc组、甲氨蝶呤+rhTNFR:Fc组骨小梁分离度明显小于0.9％氯化钠注射液组和甲氨蝶呤组(P＜0.01).结论 单用rhTNFR:Fc及联合甲氨蝶呤均具有明显抑制关节骨破坏的作用,且其抑制炎症关节周围骨量减少的作用与抑制局部骨小梁数量减少及骨小梁分离度的增大相关.
目的 通過建立膠原誘導性關節炎(CIA)大鼠模型,評價單用重組人Ⅱ型腫瘤壞死因子受體-抗體融閤蛋白(rhTNFR:Fc)及其聯閤甲氨蝶呤在抑製CIA大鼠關節骨破壞方麵的作用及機製.方法 利用皮下註射牛Ⅱ型膠原誘導Wistar大鼠髮病,建立CIA大鼠模型.將造模成功,炎癥評分≥2分的CIA大鼠隨機分為生理鹽水組(0.4 ml/週,腹腔註射)、甲氨蝶呤治療組(1 mg週,腹腔註射)、rhTN FR:Fc治療組(0.8 mg,每週2次,腹腔註射)、甲氨蝶呤+rhTN FR:Fc治療組(甲氨蝶呤1 mg/週+rhTNFR:Fc 0.8mg,每週2次,腹腔註射).治療8週後,處死大鼠,取踝關節拍攝X線片,脛骨上段行微計算機斷層掃描技術掃描和製作硬組織切片,觀察各組踝關節骨破壞情況,評價脛骨上段骨小樑變化及骨量變化.統計學處理採用SNK-q檢驗.結果 治療8週後,rhTN FR:Fc組,甲氨蝶呤+rhTNFR:Fc組骨小樑麵積百分數[(29.1±0.3)％,(26.7±0.6)％]及骨小樑數量(4.4±0.5)/mm,( 4.0±0.6 )/mm]明顯高于0.9％氯化鈉註射液組和甲氨蝶呤組[(12.9±0.5)％,( 13.2±0.4)％與(2.0±0.3 )/mm,(2.2±0.2)/mm](P＜0.01)；rhTNFR:Fc組、甲氨蝶呤+rhTNFR:Fc組骨小樑分離度明顯小于0.9％氯化鈉註射液組和甲氨蝶呤組(P＜0.01).結論 單用rhTNFR:Fc及聯閤甲氨蝶呤均具有明顯抑製關節骨破壞的作用,且其抑製炎癥關節週圍骨量減少的作用與抑製跼部骨小樑數量減少及骨小樑分離度的增大相關.
목적 통과건립효원유도성관절염(CIA)대서모형,평개단용중조인Ⅱ형종류배사인자수체-항체융합단백(rhTNFR:Fc)급기연합갑안접령재억제CIA대서관절골파배방면적작용급궤제.방법 이용피하주사우Ⅱ형효원유도Wistar대서발병,건립CIA대서모형.장조모성공,염증평분≥2분적CIA대서수궤분위생리염수조(0.4 ml/주,복강주사)、갑안접령치료조(1 mg주,복강주사)、rhTN FR:Fc치료조(0.8 mg,매주2차,복강주사)、갑안접령+rhTN FR:Fc치료조(갑안접령1 mg/주+rhTNFR:Fc 0.8mg,매주2차,복강주사).치료8주후,처사대서,취과관절박섭X선편,경골상단행미계산궤단층소묘기술소묘화제작경조직절편,관찰각조과관절골파배정황,평개경골상단골소량변화급골량변화.통계학처리채용SNK-q검험.결과 치료8주후,rhTN FR:Fc조,갑안접령+rhTNFR:Fc조골소량면적백분수[(29.1±0.3)％,(26.7±0.6)％]급골소량수량(4.4±0.5)/mm,( 4.0±0.6 )/mm]명현고우0.9％록화납주사액조화갑안접령조[(12.9±0.5)％,( 13.2±0.4)％여(2.0±0.3 )/mm,(2.2±0.2)/mm](P＜0.01)；rhTNFR:Fc조、갑안접령+rhTNFR:Fc조골소량분리도명현소우0.9％록화납주사액조화갑안접령조(P＜0.01).결론 단용rhTNFR:Fc급연합갑안접령균구유명현억제관절골파배적작용,차기억제염증관절주위골량감소적작용여억제국부골소량수량감소급골소량분리도적증대상관.
Objective This study is aimed to explore the effect of rhTNFR:Fc and methotrexate (MTX)-rhTN FR:Fc on joint destruction of collagen-induced arthritis ( CIA ) rat by establishing CIA rat model which imitates pathogenic factors of rheumatoid arthritis (RA).Methods CIA rat model were developed by subcutaneous injection of bovine type Ⅱ collagen.The rats with inflammation scores of two or above were randomly divided into four groups:the sterilized water treatment group (0.4 ml/w,intra-peritoneal injection),the MTX treatment group (1 mg/w,intra-peritoneal injection),the rhTNFR:Fc treatment group(0.8 mg Biw,intra-peritoneal injection),the MTX + rhTNFR:Fc treatment group (MTX 1 mg/w and rhTNFR:Fc 0.8 mg Biw,intraperitoneal injection).After treatment for 8 weeks,the rats were sacrificed and took the ankle radiography.Micro-CT scan of proximal tibia was performed and hard-tissue slices were made,and then the ankle's bone damage of each group was observed in order to evaluate trabecular variation and bone quantity changes of proximal tibia.Statisstical analysis was conducted with ANK-q test.Results After treatment for 8 weeks,the percentage of trabecular area and the trabecular number of the rhTNFR:Fc treatment group and the MTX-rhTNFR:Fc treatment were [(29.1±0.3)％,(26.7±0.6)％,(4.4±0.5)/mm,(4.0±0.6)/mm] (P＜0.01),which were evidently higher than the sterilized water treatment group and MTX treatment group (P＜0.01).The trabecular separation of Etanercept treatment group and MTX-rhTNFR:Fc group was obviously less than the sterilized water treatment group and MTX treatment group [(12.9±0.5)％,(13.2±0.4)％ vs (2.0±0.3)/mm,(2.2t0.2)/mm] (P＜0.01).Conclusion rhTNFR:Fc and MTX-rhTNFR:Fc can remarkably inhibit joint destruction of CIA rat.And their effect on inhibiting of inflammation and increasing peri-articular bone quantity.In addition,they are effective on inhibiting the reduction of local trabecular structure and increase of trabecular separation.
