Flt3配体对多器官功能障碍综合征小鼠脏器功能和结构的保护作用

Protective effect of Flt3 ligand on organ function and structure in mice with multiple organ dysfunction syndrome

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 observe the protective effect of Flt3 ligand （Flt3L） on organ function and structure in mice with multiple organ dysfunction syndrome （MODS）. Methods Male C57BL/6 mice were randomly divided into normal control （n = 10）, MODS （n = 30） and Flt3L treatment groups（n = 30）. MODS mice were injected with normal saline after zymosan injection. The mouse MODS models were established by intraperitoneal injection of zymosan. The mice of treatment group received 5 μg/kg Flt3L from the fifth day after zymosan injection for 7 days. The mortality rate was recorded,plasma alanine aminotransforase activity （ALT） , blood urea nitrogen （BUN） and creatinine （Cr） were determined, the subtypes of T lymphocyte were analyzed and pathological changes of the liver,lung, kidney and heart were examined. Results At 12th day after the injection of zymosan, the mortality rate of Flt3L treatment group was 7% ,lower than that of MODS group （ 18% ）. Plasma ALT, BUN and Cr levels in the MODS mice increased compared with those in normal controls, but the above mentioned parameters tended to approach normal range in the Flt3L treatment group. Marked pathological changes were noted in the liver, lungs, kidney and heart of MODS mice, including degeneration and focal necrosis of parenchyma cells. There were mild pathological changes in different organs of mice treated withFlt3L. In MODS group the number of CD4 ＋ T lymphocytes was reduced, while the number of CD8 ＋ T lymphocytes increased, and the CD4/ CD8 ratio was reduced. In the Flt3L treatment group, the number of CD4 ＋ T lymphocytes was restored to the normal level and CD4/CD8 ratio was markedly increased compared with that in the MODS mice. Conclusion Administration of Flt3L may improve the immune status and reduce the mortality rate and alleviate organ dysfunction and structure damages in mice at late phase of MODS.