乌司他丁对重症脓毒症患者的疗效及其作用机制的研究

A Study on clinical efficacy of ulinastatin in severe sepsis patients and its mechanism of action

目的 评价乌司他丁对重症脓毒症患者的疗效和安全性,并通过观察患者细胞因子的变化来探讨其作用机制。方法 56例重症脓毒症患者随机均分为乌司他丁组(U组)与对照组(C组),在相同的常规治疗基础上,U组给予乌司他丁针剂 20万U静脉注射,2次/d,持续5 d。C组则给予同等量的生理盐水作为安慰剂对照。在治疗前、治疗后 24、48、120 h进行 A PACHEⅡ评分,同时抽取右侧桡动脉血测定肿瘤坏死因子α(TNF α)、白介素1β(IL 1β)、白介素4(IL 4)、白介素6(IL 6)和白介素10(IL 10)的浓度,并统计两组患者的 28 d病死率。结果 治疗前两组患者 APACHEⅡ病情严重度评分值相似(P>0.05),治疗后两组患者APACHEⅡ评分值均有下降,但 U组患者的分值下降较 C组快。U组患者 28 d的病死率为28.6%(8/28)低于C组的57.1%(16/28),差异有显著性(P<0.05)。细胞因子检测的结果显示,U组患者的 TNF α的血清浓度在48 h内即明显下降,与 C组相比,差异有显著性(P<0.05);U组患者 IL 6 的浓度在治疗后也较 C组下降明显,并在治疗后120 h两组差异有显著性(P<0.05);U组患者 IL 10浓度在治疗后明显上升,两组差异有非常显著性(P<0.01)。结论 乌司他丁能够改善脓毒症患者的病情,降低病死率,可能与其降低脓毒症患者血中促炎因子 TNF α、IL 6 的水平,

ObjectiveTo evaluate the efficacy and safety of ulinastatin in patients with severe sepsis and investigate its mechanisms of action.MethodsFifty-six patients were randomly divided into ulinastatin treatment group (group U) and control group (group C).Patients in group U received ulinastatin 200 000 units intravenous twice a day for 5 days,while those in group C received equal quantity of normal saline as placebo.Before treatment and at 24 th 、48 th 、120 th hour after start of treatment,APACHEⅡ scores were recorded.The blood concentration of tumor necrosis factor-α(TNF-α),interleukin-1β (IL-1β),interleukin-6 (IL-6),interleukin-4 (IL-4),interleukin-10 (IL-10) were determined.Mortality rate was compared at 28 days after treatment between the two groups.ResultsThe APACHEⅡ scores in both groups decreased during the treatment,and there was significant difference between the two groups on 5 th day of treatment.The APACHEⅡscores of group U was lower than that of group C.The 28-day mortality rate was 28.6%(8/28) in group U,while that of group C was 57.1%(16/28),there was a significant difference between the two groups.No severe adverse reaction in group U was observed.The concentration of TNF-α in group U patients decreased more markedly than that in group C of 24 to 48 hours after treatment as well as IL-6 at 48 hours.However,blood concentration of TNF-α and IL-10 increased more markedly in group U than that in group C,blood level of IL-4 between the two groups were not significantly different during treatment.ConclusionsUlinastatin improves patient’s condition and reducing 28-day mortality of severe sepsis patients.Ulinastatin can decrease the blood concentration of TNF-α and IL-6 and increase the blood level of IL-10 in patients with severe sepsis.It is a safe and affordable drug for the treatment of severe sepsis.