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目的:建立pristane诱导的系统性红斑狼疮(SLE)小鼠模型,并对该小鼠模型的发病机制进行初步的探讨。方法:6-8周龄雌性BALB/c小鼠单次腹腔注射pristane0.5mL,对照组单次腹腔注射PBS0.5mL,注射前及注射后每2周行流式细胞术(FCM)检测外周血中IFN-α分泌细胞(CD11b+Ly6Chigh)的比例及细胞活化状态B220+Aβ1dhigh),ELISA检测血清中自身抗体(anti-dsDNA,anti-smRNP,anti-ribosomalP0)的含量。至6个月处死动物,FCM检测腹腔细胞中IFN-α分泌细胞(CD11b+Ly6Chigh)的比例和脾脏中细胞的活化(B220,Aβ1d),采用直接免疫荧光法标记小鼠肾脏免疫球蛋白复合物及H&E染色评估小鼠肾脏免疫复合物的沉积及损伤情况。结果:小鼠腹腔注射pristane第2个月开始血清总IgG升高,第3个月起出现自身抗体阳性,到个6月时达到最高,并维持高水平至被处死;Pristane处理6个月后,Pristane处理组小鼠出现关节炎症状,肾脏免疫复合物的大量沉积和明显肾脏损伤。Pristane注射2周起,小鼠外周血中IFN-α分泌细胞(CD11b+Ly6Chigh)的比例明显高于PBS注射组,小鼠腹腔细胞中IFN-α分泌细胞的比例也明显升高;同时外周血和脾细胞中B细胞表面MHCII分子Aβ1d的平均荧光强度(MFI)均高于对照组,表明pristane处理组小鼠中B细胞发生了显著活化。结论:BALB/c小鼠腹腔注射pristane可诱导构建小鼠SLE模型,其SLE的发病可能与IFN-α的持续分泌导致B细胞的异常活化有关。该模型的建立为进一步研究SLE的发病机制提供了良好的动物模型。
Objective: To establish pristane-induced mouse model of systemic lupus erythematosus (SLE) and to investigate the pathogenesis of this mouse model. Methods: Female BALB / c mice (6-8 weeks old) were injected intraperitoneally with 0.5 ml of pristane, 0.5 ml of PBS was injected intraperitoneally into the control group. Before and 2 weeks after injection, the levels of IFN in peripheral blood were measured by flow cytometry (FCM) α secreting cells (CD11b + Ly6Chigh) and the cell activation state B220 + Aβ1dhigh) were detected by enzyme-linked immunosorbent assay (ELISA). The levels of anti-dsDNA, anti-smRNP and anti- The animals were sacrificed at 6 months. The proportion of IFN-α secreting cells (CD11b + Ly6Chigh) and the activation of cells in the spleen (B220, Aβ1d) in peritoneal cells were determined by FCM. The mouse kidney immunoglobulin complex was labeled by direct immunofluorescence And H & E staining to evaluate the deposition and injury of mouse kidney immune complexes. Results: The total serum IgG increased from the second month of pristane injection to the first month of autoimmunity. The positive rate of autoantibodies appeared at the third month and reached the highest at the sixth month after the pristane injection. , The mice in the Pristane treated group developed symptoms of arthritis, massive deposits of renal immune complexes, and significant kidney damage. The ratio of IFN-α-secreting cells (CD11b + Ly6Chigh) in mice peripheral blood was significantly higher than that in PBS-injected mice at 2 weeks after Pristane injection. The proportion of IFN-α-secreting cells in peritoneal cells of mice also increased significantly. And mean fluorescence intensity (MFI) of MHCII molecule Aβ1d on B cells in splenocytes were higher than those in control group, indicating that B cells in pristane-treated mice were significantly activated. Conclusion: The intraperitoneal injection of pristane in BALB / c mice can induce the formation of SLE model in mice. The onset of SLE may be related to the persistent secretion of IFN-α resulting in the abnormal activation of B cells. The establishment of this model provides a good animal model for further studying the pathogenesis of SLE.