滤泡辅助性T细胞在急性肝衰竭小鼠模型中的变化及意义

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目的:探讨滤泡辅助性T(T follicular helper,Tfh)细胞及相关细胞因子白细胞介素(interleukin,IL)-21在急性肝衰竭(acute liver failure,ALF)小鼠模型中的变化及意义。方法:将20只雌性C57BL/6小鼠随机分成2组,分别予脂多糖/D-氨基半乳糖或磷酸盐缓冲液(phosphate buffer solution,PBS)腹腔注射,6 h后采集血液、肝脏和脾脏组织标本。采用苏木精-伊红染色法分析肝脏病变情况;流式细胞术分析小鼠脾脏单个核细胞中Tfh细胞的频数;酶联免疫吸附试验分析血清中IL-21和肿瘤坏死因子α(tumor necrosis factorα,TNF-α)的水平。结果:ALF小鼠肝脏肿大而呈暗红色,肝细胞大量坏死和炎性细胞浸润,其血清中TNF-α及IL-21的水平均较正常对照组显著增高(P<0.01,P<0.05);而单个核细胞中CD4+CXCR5+、CD4+PD-1+、CD4+CXCR5+PD-1+T细胞频数亦较正常对照组显著升高(P<0.01)。结论:ALF小鼠脾脏单个核细胞中Tfh细胞频数显著增加,血清IL-21水平显著升高,推测Tfh细胞在ALF的发病过程中起重要作用,本研究结果可能为ALF的治疗提供新思路。 Objective: To investigate the changes and significance of T follicular helper (Tfh) cells and related cytokines interleukin (IL) -21 in mice with acute liver failure (ALF). Methods: Twenty female C57BL / 6 mice were randomly divided into two groups, which were injected intraperitoneally with lipopolysaccharide / D-galactosamine or phosphate buffer solution (PBS). Blood, liver and spleen Tissue samples. The hepatic lesions were analyzed by hematoxylin-eosin staining. The frequency of Tfh cells in spleen mononuclear cells was analyzed by flow cytometry. The levels of IL-21 and tumor necrosis factor alpha, TNF-alpha) levels. Results: The liver of ALF mice was swollen and dark red with large necrosis of hepatocytes and inflammatory cell infiltration. The levels of TNF-α and IL-21 in serum of ALF mice were significantly higher than those of normal control group (P <0.01, P <0.05 ). The frequencies of CD4 + CXCR5 +, CD4 + PD-1 +, CD4 + CXCR5 + PD-1 + T cells in mononuclear cells were significantly higher than those in normal control group (P <0.01). CONCLUSIONS: The frequency of Tfh cells in spleen mononuclear cells of ALF mice increased significantly and the level of serum IL-21 was significantly increased. It is speculated that Tfh cells play an important role in the pathogenesis of ALF. The results of this study may provide new ideas for the treatment of ALF.
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