目的:讨论乌司他丁对脓毒症大鼠肾脏细胞凋亡机制研究。方法:健康30只雄性SD大鼠随机分成3组:正常组(Sham组,10只)、脓毒症组(Sepsis组,10只)、乌司他丁组(UTI组,10只)。Sham组仅行开腹、关腹手术,Sepsis组和UTI组采用盲肠结扎穿孔术(CLP)制作脓毒症大鼠模型,建模成功后15min在UTI组大鼠尾静脉注射乌司他丁(20万U/kg),12h后重复给药,Sham组与Sepsis组则在相同的时间点注射等量的生理盐水。于6、12、24、36、48h尾静脉采血应用酶联免疫吸附试验(ELISA)检测血清中肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)的质量浓度,留取肾脏标本行苏木精-伊红染色观察组织病理变化;通过免疫组织化学法检测凋亡蛋白Bax和Caspase-3在肾组织内表达情况。结果:在Sepsis组中炎性因子TNF-α和IL-6均在12h达到峰值,相对于UTI组TNF-α和IL-6差异明显。在UTI组6、12、24、36、48h炎性因子IL-6和TNF-α表达均明显低于Sepsis组(P<0.05)。在苏木精-伊红染色中发现UTI组较Sepsis组肾脏细胞肿胀及出血明显减轻、炎性细胞浸润减少;免疫组织化学检测发现UTI组中Bax蛋白表达明显低于Sepsis组,UTI组中Caspase-3蛋白表达明显低于Sepsis组(P<0.05)。结论:乌司他丁抑制脓毒症大鼠炎症反应同时抑制肾脏以线粒体途径的Caspase通路细胞凋亡,对肾脏有一定保护作用。 Objective: To investigate the mechanism of ulinastatin on renal cell apoptosis in septic rats. Methods: Thirty healthy male Sprague-Dawley rats were randomly divided into three groups: normal group (Sham group, 10 rats), sepsis group (10 rats) and ulinastatin group (UTI group, 10 rats). The rats in Sham group underwent laparotomy only, the abdomen was closed, the sepsis group and the UTI group were made by cecal ligation and puncture (CLP) to establish the sepsis rat model, and the rats in UTI group were injected with ulinastatin 200 000 U / kg), repeated administration after 12h, Sham group and Sepsis group were injected with the same amount of saline at the same time point. Serum levels of TNF-α and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA) at 6, 12, 24, 36, Kidney specimens were stained with hematoxylin-eosin for histopathological changes. The expression of Bax and Caspase-3 in renal tissues was detected by immunohistochemistry. Results: The levels of TNF-α and IL-6 in Sepsis group peaked at 12h, which was significantly different from that in UTI group. The expression of IL-6 and TNF-αin 6, 12, 24, 36, and 48 h in UTI group were significantly lower than those in Sepsis group (P <0.05). In hematoxylin-eosin staining, the swelling and hemorrhage of renal cells in UTI group were significantly reduced and the infiltration of inflammatory cells was reduced in UTI group. Immunohistochemistry showed that the expression of Bax protein in UTI group was significantly lower than that in Sepsis group and in UTI group -3 protein expression was significantly lower than Sepsis group (P <0.05). Conclusion: Ulinastatin can inhibit the inflammatory response of septic rats and inhibit the apoptosis of the kidney in the mitochondrial pathway of Caspase pathway, which may have a protective effect on the kidney.