CAJ | 학술논문

目的观察体外扩增的骨髓源间充质干细胞联合同种异体骨髓移植治疗狼疮模型鼠的疗效,并探讨其在系统性红斑狼疮发病机制中的作用.方法将20只鼠龄为12周的雌性狼疮模型鼠按随机数字表法随机分为单纯骨髓移植组、联合Ⅰ组、联合Ⅱ组、阳性对照组,并设雄性BALB/c小鼠为阴性对照组.将体外扩增的BALB/c小鼠骨髓源问充质干细胞联合雄性C57BL/6小鼠骨髓植入狼疮模型鼠体内,测移植1个月后小鼠体内的Y染色体,并通过小鼠的体重、白细胞、尿蛋白、抗双链DNA抗体水平及终期小鼠肾脏病理和免疫荧光来评价移植的疗效.结果 (1)移植30 d后,可在狼疮模型鼠体内检测到Y染色体,表明移植成功.(2)单纯骨髓移植组、联合Ⅰ组、联合Ⅱ组小鼠尿蛋白和抗双链DNA抗体水平均显著下降.移植40 d后联合Ⅰ组、联合Ⅱ组抗双链DNA抗体吸光度(A)值分别为0.76±0.28、0.73±0.10,与阴性对照组(0.47±0.10)相比,差异无统计学意义(P>0.05);单纯骨髓移植组抗双链DNA抗体水平虽有明显下降(0.91±0.27),但仍高于阴性对照组,差异有统计学意义(P<0.05).移植50 d后单纯骨髓移植组抗双链DNA抗体A值为0.55±0.15,与阴性对照组相比差异无统计学意义(P>0.05).(3)各组接受移植的小鼠肾脏病理光镜下基本恢复正常,未见炎性细胞浸润及血管坏死.免疫荧光强度均弱于阳性对照组.结论单纯骨髓移植和联合问充质干细胞移植均能有效改善狼疮模型鼠的病情;间充质干细胞可加速狼疮模型鼠外周血抗双链DNA抗体和肾脏免疫复合物的清除,帮助受损器官的恢复.
목적 관찰체외확증적골수원간충질간세포연합동충이체골수이식치료랑창모형서적료효,병탐토기재계통성홍반랑창발병궤제중적작용.방법 장20지서령위12주적자성랑창모형서안수궤수자표법수궤분위단순골수이식조、연합Ⅰ조、연합Ⅱ조、양성대조조,병설웅성BALB/c소서위음성대조조.장체외확증적BALB/c소서골수원문충질간세포연합웅성C57BL/6소서골수식입랑창모형서체내,측이식1개월후소서체내적Y염색체,병통과소서적체중、백세포、뇨단백、항쌍련DNA항체수평급종기소서신장병리화면역형광래평개이식적료효.결과 (1)이식30 d후,가재랑창모형서체내검측도Y염색체,표명이식성공.(2)단순골수이식조、연합Ⅰ조、연합Ⅱ조소서뇨단백화항쌍련DNA항체수평균현저하강.이식40 d후연합Ⅰ조、연합Ⅱ조항쌍련DNA항체흡광도(A)치분별위0.76±0.28、0.73±0.10,여음성대조조(0.47±0.10)상비,차이무통계학의의(P>0.05);단순골수이식조항쌍련DNA항체수평수유명현하강(0.91±0.27),단잉고우음성대조조,차이유통계학의의(P<0.05).이식50 d후단순골수이식조항쌍련DNA항체A치위0.55±0.15,여음성대조조상비차이무통계학의의(P>0.05).(3)각조접수이식적소서신장병리광경하기본회복정상,미견염성세포침윤급혈관배사.면역형광강도균약우양성대조조.결론 단순골수이식화연합문충질간세포이식균능유효개선랑창모형서적병정;간충질간세포가가속랑창모형서외주혈항쌍련DNA항체화신장면역복합물적청제,방조수손기관적회복.
In order to study the role of the bone marrow-derived mesenchymal stem cells(MSCs)transplanted with or without bone marrow(BM)in the treatment of lupus mice and the effect of MSCs in the onset of systemic lupus erythematosus(SLE).Method Twenty 12-week-old female MRL/lpr mice were randomly divided into four groups,including simple bone marrow transplantation group(SG,BM 1×107),united group-1(UG1,BM 1×107+MSCs 1×104),united group-2(UG2,BM 1×107+MSCs 1×106),the positive control group(PG,no transplantation).BALB/c mice were used as the negative control group(NG,no transplantation).MSCs which were amplified from the bone marrow of male BALB/c mice in vitro were transplanted into the female MRL/lpr mice with or without BM.One month later Y chromosome was detected to confirm if the transplantation was successful or not.The change of weight, white blood cells,urine protein,anti-dsDNA antibody,the pathology and immunofluorescence of renal were observed to evaluate the therapeutic efficacy.Results Y chromosome was detected in all transplanted female mice.Compared with PG,urine protein concentration in SG,UG1 and UG2 significantly decreased 30 days after transplantation(P<0.05).40 days after transplantation,the rite of anti-dsDNA antibodies in sG(0.91±0.27)was still higher than NG,which OD value wag 0.47 s0.10(P<0.05),but there was no statistical difference among UG1(0.76±0.28),uG2(0.73±0.10)and NG(P>0.05).However,50 days after transplantation,there was no marked difference of the tite of anti-dsDNA antibodies in SG(0.55±0.15),UG1(0.57±0.14)and UC2(0.58±0.05)compared with NG(P>0.05).After transplantation there was no vasculitis.no inflammatory cell infiltration in matrix and no obvious intercapillary cells proliferation in the kidney.The immunofluoroscence became negative or weakly positive.Conclusion MSCs transplantation with or without BM Can both improve the pathogenetic condition of MRL/lpr mice.MSCs can accelerate the clearance of anti-dsDNA antibody and promote the restoration of injured organs.We presume that MSCs are important immunological regulation cells in SLE.