乌司他丁对脓毒症小鼠生存率及淋巴细胞凋亡的影响

Impact of ulinastatin on survival and lymphocyte apoptosis in septic mice

目的观察乌司他丁(UTI)对脓毒症小鼠生存率及淋巴细胞凋亡的影响,探讨UTI对脓毒症的可能作用机制。方法 8～10周C57BL/6雄性小鼠40只,随机分成4组:假手术(Sham)组,盲肠结扎穿孔(CLP)组,CLP+UTI(10万U/kg)术后30 min腹腔内给药(UTI ip)组和CLP+UTI(10万U/kg)术后30 min尾静脉给药(UTI iv)组。在CLP模型建立成功后,每组10只小鼠首先进行7 d生存状况观察研究,描绘7 d生存曲线。另选取40只小鼠按以上方法分组,在CLP术后24 h取材,计数外周血、胸腺和脾脏淋巴细胞,检测胸腺和脾脏淋巴细胞凋亡情况。数据采用Prism5.01(GraphPad Software,USA)软件包进行统计学处理。结果 UTI治疗组7 d生存率高于CLP组,差异有统计学意义(P<0.05)。UTI组外周血、胸腺和脾脏淋巴细胞计数高于CLP组,差异有统计学意义(P<0.05);UTI组脓毒症小鼠胸腺和脾脏淋巴细胞凋亡低于CLP组,差异有统计学意义(P<0.05)。UTI ip和UTI iv组之间各项指标差异均无统计学意义。结论应用UTI腹腔或尾静脉给药可明显改善脓毒症小鼠的生存状况,可能与其升高脓毒症小鼠外周血、胸腺和脾脏淋巴细胞数量,有效降低脓毒症小鼠胸腺和脾脏组织淋巴细胞凋亡等有关。

Objective To observe the effect of ulinastatin on the survival and lymphocyte apoptosis in mice with cecal ligation and puncture（CLP） induced sepsis,so as to investigate the possible mechanism of ulinastatin action in sepsis.Methods Forty 8-10 weeks old male C57BL/6 mice（22-30 g body weight） were randomly assigned to four groups,i.e.,Sham group,CLP group,CLP plus UTI ip group（100 000 U/kg by intraperitoneal injection at half an hour after operation）,and CLP plus UTI iv group（100 000 U/kg by intravenous injection at half an hour after operation）.After successful establishment of CLP model,the 7-day survival of the 10 animals in each group was observed and the survival curve was also plotted.Based on the 7-day survival of animals,another 40 mice were divided into the above 4 groups and specimens were collected 24 h after CLP to examine the lymphocyte count in the peripheral blood,thymus and spleen and the apoptosis of lymphocytes in the thymus and spleen.The statistical analyses were done with Prism5.01（GraphPad Software,USA）.Results The 7-day survival rates in the two UTI groups were significantly higher than that in the CLP group（P0.05）.The lymphocyte counts in the two UTI groups were significantly higher than that in the CLP group（P0.05）,and the lymphocyte apoptosis rates in the two UTI groups were significantly lower than that in the CLP group（P0.05）.The above parameters were not significantly different between the two UTI groups.Conclusion Both intraperitoneal and intravenous treatment with UTI can greatly improve the survival of septic mice,which might be related to the roles of UTI in increasing the lymphocytes count in the peripheral blood,thymus and spleen of septic mice and in alleviating lymphocyte apoptosis in the thymus and spleen.