中华风湿病学杂志
中華風濕病學雜誌
중화풍습병학잡지
Chinese Journal of Rheumatology
2015年
10期
682-685,封3
,共5页
关节炎,实验性%核因子-κB%三氧化二砷
關節炎,實驗性%覈因子-κB%三氧化二砷
관절염,실험성%핵인자-κB%삼양화이신
Arthritis,exprimental%NF-κB%Arsenic trioxide
目的 评估腹腔注射三氧化二砷(ATO)对胶原诱导性关节炎(CIA)大鼠关节症状的改善程度,观察其对CIA大鼠血清NF-κB受体活化因子配体(RANKL)、骨保护素(OPG)水平的影响,并探讨其对NF-κB受体活化因子(RANK)/RANKL/OPG系统的作用机制.方法 将28只体质量及鼠龄相当的Wistar大鼠依次编号,用随机数字表法选取8只为对照组(A组),剩余20只为造模组(用牛Ⅱ型胶原和弗氏完全佐剂乳化液免疫动物2次,成功建立CIA大鼠模型16只),造模成功后应用随机数字表法将其分为CIA模型对照组8只、三氧化二砷治疗组8只;三氧化二砷治疗组在分组3d后通过腹腔注射三氧化二砷液1周,剂量4 mg· kg-1·d-1,最后1d给予8 mg/kg,观察3d取材,对照组以同样方法给予等容量的0.9％氯化钠注射液.对各组大鼠定期进行关节炎指数(AI)评定以及四肢关节X线摄片评估关节破坏程度.各组大鼠干预结束后内眦静脉取血,用流式细胞术(FMC)对各组大鼠血清中核RANKL、骨保护素进行定量测定.应用t检验或对各组应用Wilcoxon秩和检验进行组间比较.结果 ①腹腔注射三氧化二砷液1周后大鼠AI较同期CIA模型组明显改善(分别为2.63±0.92,6.62±0.91),差异有统计学意义(t=8.73,P＜0.01),X线显示关节破坏程度减轻.②CIA模型组血清中RANKL水平明显高于同期空白对照组[1 890.70 (797.03,10 571.94) pg/ml,74.46 (29.21,95.37) pg/ml],差异有统计学意义(T=43,P=0.005).③三氧化二砷治疗组与同期CIA模型组相比RANKL水平明显降低[44.78(21.41,79.83) pg/ml,1 890.70(797.03,10 571.94) pg/ml],差异有统计学意义(T=47,P=0.01).④3组间血清骨保护素水平相当[16.87(6.91,17.64) pg/ml,5.32 (3.42,33.14) pg/ml,14.24 (6.96,21.86) pg/ml],差异无统计学意义(x2=5.078,P=0.166).结论 CIA大鼠在骨代谢过程中存在炎性介质紊乱,血清中RANKL/OPG浓度比升高;腹腔注射三氧化二砷可以改善CIA大鼠的关节炎程度,其作用机制可能通过下调血清RANKL/OPG浓度比来发挥作用.
目的 評估腹腔註射三氧化二砷(ATO)對膠原誘導性關節炎(CIA)大鼠關節癥狀的改善程度,觀察其對CIA大鼠血清NF-κB受體活化因子配體(RANKL)、骨保護素(OPG)水平的影響,併探討其對NF-κB受體活化因子(RANK)/RANKL/OPG繫統的作用機製.方法 將28隻體質量及鼠齡相噹的Wistar大鼠依次編號,用隨機數字錶法選取8隻為對照組(A組),剩餘20隻為造模組(用牛Ⅱ型膠原和弗氏完全佐劑乳化液免疫動物2次,成功建立CIA大鼠模型16隻),造模成功後應用隨機數字錶法將其分為CIA模型對照組8隻、三氧化二砷治療組8隻;三氧化二砷治療組在分組3d後通過腹腔註射三氧化二砷液1週,劑量4 mg· kg-1·d-1,最後1d給予8 mg/kg,觀察3d取材,對照組以同樣方法給予等容量的0.9％氯化鈉註射液.對各組大鼠定期進行關節炎指數(AI)評定以及四肢關節X線攝片評估關節破壞程度.各組大鼠榦預結束後內眥靜脈取血,用流式細胞術(FMC)對各組大鼠血清中覈RANKL、骨保護素進行定量測定.應用t檢驗或對各組應用Wilcoxon秩和檢驗進行組間比較.結果 ①腹腔註射三氧化二砷液1週後大鼠AI較同期CIA模型組明顯改善(分彆為2.63±0.92,6.62±0.91),差異有統計學意義(t=8.73,P＜0.01),X線顯示關節破壞程度減輕.②CIA模型組血清中RANKL水平明顯高于同期空白對照組[1 890.70 (797.03,10 571.94) pg/ml,74.46 (29.21,95.37) pg/ml],差異有統計學意義(T=43,P=0.005).③三氧化二砷治療組與同期CIA模型組相比RANKL水平明顯降低[44.78(21.41,79.83) pg/ml,1 890.70(797.03,10 571.94) pg/ml],差異有統計學意義(T=47,P=0.01).④3組間血清骨保護素水平相噹[16.87(6.91,17.64) pg/ml,5.32 (3.42,33.14) pg/ml,14.24 (6.96,21.86) pg/ml],差異無統計學意義(x2=5.078,P=0.166).結論 CIA大鼠在骨代謝過程中存在炎性介質紊亂,血清中RANKL/OPG濃度比升高;腹腔註射三氧化二砷可以改善CIA大鼠的關節炎程度,其作用機製可能通過下調血清RANKL/OPG濃度比來髮揮作用.
목적 평고복강주사삼양화이신(ATO)대효원유도성관절염(CIA)대서관절증상적개선정도,관찰기대CIA대서혈청NF-κB수체활화인자배체(RANKL)、골보호소(OPG)수평적영향,병탐토기대NF-κB수체활화인자(RANK)/RANKL/OPG계통적작용궤제.방법 장28지체질량급서령상당적Wistar대서의차편호,용수궤수자표법선취8지위대조조(A조),잉여20지위조모조(용우Ⅱ형효원화불씨완전좌제유화액면역동물2차,성공건립CIA대서모형16지),조모성공후응용수궤수자표법장기분위CIA모형대조조8지、삼양화이신치료조8지;삼양화이신치료조재분조3d후통과복강주사삼양화이신액1주,제량4 mg· kg-1·d-1,최후1d급여8 mg/kg,관찰3d취재,대조조이동양방법급여등용량적0.9％록화납주사액.대각조대서정기진행관절염지수(AI)평정이급사지관절X선섭편평고관절파배정도.각조대서간예결속후내자정맥취혈,용류식세포술(FMC)대각조대서혈청중핵RANKL、골보호소진행정량측정.응용t검험혹대각조응용Wilcoxon질화검험진행조간비교.결과 ①복강주사삼양화이신액1주후대서AI교동기CIA모형조명현개선(분별위2.63±0.92,6.62±0.91),차이유통계학의의(t=8.73,P＜0.01),X선현시관절파배정도감경.②CIA모형조혈청중RANKL수평명현고우동기공백대조조[1 890.70 (797.03,10 571.94) pg/ml,74.46 (29.21,95.37) pg/ml],차이유통계학의의(T=43,P=0.005).③삼양화이신치료조여동기CIA모형조상비RANKL수평명현강저[44.78(21.41,79.83) pg/ml,1 890.70(797.03,10 571.94) pg/ml],차이유통계학의의(T=47,P=0.01).④3조간혈청골보호소수평상당[16.87(6.91,17.64) pg/ml,5.32 (3.42,33.14) pg/ml,14.24 (6.96,21.86) pg/ml],차이무통계학의의(x2=5.078,P=0.166).결론 CIA대서재골대사과정중존재염성개질문란,혈청중RANKL/OPG농도비승고;복강주사삼양화이신가이개선CIA대서적관절염정도,기작용궤제가능통과하조혈청RANKL/OPG농도비래발휘작용.
Objective To assess the improvement of articular symptoms on collagen induced arthritis (CIA) rats after injecting arsenic trioxide (ATO) intraperitoneal and observe its effects on serum RANKL, OPG on CIA rats and discuss the possible mechanism on RANK/RANKL/OPG system.Methods Numberd twentyeight Wistar rats with correspond weight and age consecutively, then using random number table select 8 rats as blank control group A.Another other 20 as model group (16 wistar rats are established as CIA models by immunized twice with bovine type Ⅱ collagen and Freund's complete adjuvant emulsion).Using ranllm numbor table divided CIA rast into the CIA model control group B (n=8) and ATO treatment group C (n=8) randomly.After grouping for 3 days, ATO treatment group were injected with ATO liquid intraperitoneally for 1 week (dose of 4 mg· g-1·d-1, last 1 day raise to 8 mg/kg).Serum were collected after 3 days , while rates in the control group were given same quantity of saline solution with the same method.Arthritis index (AI) and X-ray radiography were assessed for limb joint damage.Flow cytometry (FMC) was used to detect chemokines quantitatively of each rats serum, including Nuclear factor kappa B ligand receptor activation factor/bone protection predominate (RANKL/OPG).According to the data distribution, t test or Wilcoxon test were used to compare the difference between groups.Results ① After administration with ATO for 1 week arthritis index of group C reduced significantly than the CIA model group (2.63±0.92, 6.62±0.91, t=8.73, P＜0.01), and X-ray showed joint damage alleviated.② The serum level of RANKL in the CIA model group was significantly higher than the blank control group [(1 890.70(797.03, 10 571.94) pg/ml, 74.46(29.21, 95.37) pg/ml, T=43, P=0.005];③ The serum level of RANKL in the ATO treatment group was significantly lower than the CIA model group [44.78 (21.41, 79.83), 1 890.70 (797.03, 10 571.94), T=47, P=0.01].④ There was no statistically significant difference of the Serum OPG level between the three groups [16.87(6.91, 17.64), 5.32(3.42, 33.14),14.24(6.96, 21.86) pg/ml, x2=5.078, P=0.166].Conclusion The inflammatory mediators in the process of bone metabolism of CIA rats is disordered , the most significant presentation is the rise of serum RANKL level.Intraperitoneal injection of ATO could improve the arthritis index of CIA rats and its mechanism may be reducing the concentration of serum RANKL/OPG ratio.
