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目的观察Flt3配体(Flt3L)对酵母多糖致多器官功能障碍综合征(multiple organ dysfunc-tion syndrome,MODS)小鼠多脏器功能和结构损伤的防护作用。方法采用腹腔注射酵母多糖的方法复制小鼠MODS模型。雄性C57BL/6小鼠随机分为正常组(n=10),MODS组(n=30)和Flt3L治疗组(n=30)。MODS组在致伤后腹腔注入生理盐水;Flt3L治疗组在致伤后第5 d起腹腔注射Flt3配体(5μg/kg),连续给药7 d。观察酵母多糖致伤12 d动物死亡率,检测各组血丙氨酸转氨酶活性(alanine aminotransforase activity,ALT)、尿素氮(blood urea nitrogen,BUN)和肌酐(cre-atinine,Cr)水平,外周血T淋巴细胞亚群变化,镜下观察致伤后12 d动物肝、肺、肾、心等脏器的组织病理学改变。结果在酵母多糖致伤后12 d,MODS组小鼠死亡率达18%,Flt3L治疗组的小鼠死亡率为7%。MODS组小鼠血浆AIT、BUN和Cr在伤后12 d升高,而同时间点经Flt3L治疗的小鼠血浆AIT、BUN和Cr趋于正常,明显低于MODS组。MODS组小鼠肝脏、肺脏、肾脏和心脏发生明显的病理改变,主要表现为脏器实质细胞多呈变性与灶状坏死改变,而Flt3L治疗组小鼠上述病变明显减轻。MODS组小鼠CD4+T细胞数目减少,而CD8+T细胞数目呈明显增高,CD4/CD8比值显著下降;而Flt3L治疗组CD4+T细胞数目增加恢复至正常水平,CD4/CD8比值较MODS组明显上调。结论给予Flt3L可以改善机体免疫状态,降低MODS期动物的死亡率,减轻脏器功能和结构的损伤,对MODS期的脏器损伤具有保护作用。
Objective To investigate the protective effect of Flt3 ligand (Flt3L) on multiple organ dysfunc- tion syndrome (MODS) induced multiple organ dysfunction and structural damage in mice. Methods The mouse model of MODS was reproduced by intraperitoneal injection of zymosan. Male C57BL / 6 mice were randomly divided into normal group (n = 10), MODS group (n = 30) and Flt3L treatment group (n = 30). Rats in MODS group were injected intraperitoneally with saline after injury; Flt3L treatment group was injected intraperitoneally with Flt3 ligand (5μg / kg) on day 5 after injury for 7 days. To observe the animal mortality caused by zymosan on day 12, the levels of alanine aminotransforase activity (ALT), blood urea nitrogen (BUN) and cre-atinine (Cr) T lymphocyte subsets. The histopathological changes of liver, lung, kidney, heart and other organs were observed 12 days after injury. Results The mortality rate of mice in MODS group was 18% after 12 days of yeast polysaccharide injury, and the mortality rate of mice in Flt3L treatment group was 7%. The levels of AIT, BUN and Cr in plasma of MODS group increased 12 d after injury, while AIT, BUN and Cr in plasma of mice treated with Flt3L at the same time point tended to be normal, which was significantly lower than that in MODS group. The liver, lung, kidney and heart of MODS group showed obvious pathological changes, mainly manifested as the degeneration and focal necrosis of parenchymal cells in organ, while the mice in the Flt3L treatment group were significantly reduced. The number of CD4 + T cells in MODS group was decreased, but the number of CD8 + T cells was significantly increased and the ratio of CD4 / CD8 was significantly decreased; while the number of CD4 + T cells in Flt3L treatment group increased back to normal level, Significantly increased. Conclusion The administration of Flt3L can improve the immune status, reduce the animal mortality in MODS, reduce the function and structure of organ damage, and protect MODS organ injury.