首页|微小RNA-7缺乏对DSS诱导小鼠急性溃疡性结肠炎模型外周免疫细胞组成的影响

微小RNA-7缺乏对DSS诱导小鼠急性溃疡性结肠炎模型外周免疫细胞组成的影响

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目的 本研究旨在探讨微小RNA-7(miR-7)对于采用葡聚糖硫酸钠盐(DSS)诱导的急性溃疡性结肠炎(UC)模型小鼠外周免疫器官脾脏和肠系膜淋巴结(MLNs)中免疫细胞比例的影响,并初步探讨其生物学意义。方法 实验中采用miR-7基因敲减(Knockdown,KD)转基因小鼠,利用DSS诱导建立UC模型,进而观察其脾脏和MLNs形态、重量、细胞总数及病理组织学变化;利用流式细胞术(FCM)检测小鼠外周免疫器官脾脏和MLNs中 CD19+B细胞、CD8+T细胞和CD4+T细胞等适应性免疫细胞及固有免疫细胞(Gr-1+中性粒细胞、CD11b+细胞、NK1。1+T细胞、CD11c+树突状细胞、F4/80+巨噬细胞、γδ T细胞)的比例并计算细胞绝对数。结果 与野生型(WT)UC模型小鼠相比,miR-7KD的UC模型小鼠的脾脏和肠系膜淋巴结形态、体积明显增大,重量显著增加(P<0。05),细胞总数显著增高(P<0。05)。HE染色结果显示,较WTUC模型小鼠组,miR-7KD UC模型小鼠组的脾窦扩张充血,脾小结减小;肠系膜淋巴结显示淋巴滤泡明显增大,髓质区和皮质区扩张。在miR-7基因敲除小鼠中,脾脏和MLNs中 CD4+T细胞、CD8+T细胞、CD19+B细胞的细胞数量均明显增加,差异具有统计学意义(P<0。05);同时,固有免疫细胞Gr-1+中性粒细胞、CD11b+细胞、CD11c+树突状细胞、F4/80+巨噬细胞和γδT细胞数均明显增加(P<0。05)。结论 miR-7敲减显著改变小鼠外周免疫器官脾脏和MLNs中病理组织学结构和免疫细胞的组成,这表明miR-7可能通过调节外周免疫细胞变化来介导UC的病理损伤进程,为深入研究UC等炎症性疾病的发病机制提供了有力的支持。这一发现不仅强调miR-7在免疫反应中的重要性,还为未来治疗策略的制定提供了潜在的理论基础。
Effect of microRNA-7 knockdown on peripheral immune cell composition in DSS-induced murine ulcerative colitis model
Objective To determine whether microRNA-7(miRNA-7,miR-7)alters the proportion of immune cells in peripheral immune organs such as the spleen and mesenteric lymph nodes(MLNs),in dextran sulfate sodium salt(DSS)-induced ulcerative colitis(UC)mice,and to explore its initial significance.Methods An a-cute UC model was established in miR-7 knockdown(KD)transgenic mice using DSS.The morphology and weight of the spleen and MLNs,as well as the total cell numbers,were observed;flow cytometry(FCM)was performed to identify the proportions of adaptive immune cells(CD19+B cells,CD4+T cells and CD8+T cells)and innate immune cells(Gr-1+neutrophils,CD11b+cells,NK1.1+T cells,CD11c+dendritic cells,F4/80+macrophages and γδ T cells)in spleen and MLNs of the peripheral immune organs in mice,and to cal-culate the absolute cell numbers.Results Compared to wild-type(WT)UC model mice,miR-7KD UC model mice exhibited significantly larger spleens and MLNs,with a notable increase in both weight and cell number(P<0.05).There was a significant increase in CD4+T cells,CD8+T cells,and CD19+B cells among them(P<0.05).The results of HE staining showed that,compared to the WT UC model mice,the miR-7KD UC model mice exhibited dilated and congested splenic sinuses and reduced spleen nodules.Additionally,the mesenteric lymph nodes in the miR-7KD UC model mice displayed significantly enlarged lymphoid follicles and expanded medullary and cortical areas.In miR-7 knockdown mice,the number of CD4+T cells,CD8+T cells,and CD19+B cells in the spleen and MLNs significantly increased,with the differences being statistically significant(P<0.05).Additionally,the numbers of innate immune cells,including Gr-1+neutrophils,CD11b+cells,CD11c+dendritic cells,F4/80+macrophages,and γ8T cells,were also significantly elevated(P<0.05).Conclusion miR-7 knockdown significantly altered the composition of immune cells in the spleen and MLNs of peripheral immune organs in mice,suggesting that miR-7 may mediate the pathological damage in UC by affect-ing the changes of peripheral immune cells.These findings provide preliminary data for understanding the patho-genesis of clinically relevant inflammatory diseases,such as UC.

miR-7 knockdownulcerative colitisperipheral immune organsimmune cells

代腾堃、赵家敏、梁易丹、李欣、赵娟娟

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贵州省基因检测与治疗特色重点实验室暨贵州省生物治疗人才基地,贵州遵义 563006

遵义医科大学免疫学教研室,贵州遵义 563006

miR-7基因敲减 溃疡性结肠炎 外周免疫器官 免疫细胞

国家自然科学基金资助项目贵州省科学技术基金重点资助项目遵义医科大学研究生科研基金项目

82360018QKHJC-ZK2022623ZYK207

2024

遵义医科大学学报
遵义医科大学

遵义医科大学学报

CSTPCD
ISSN:2096-8159
年,卷(期):2024.47(10)