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目的 研究乌司他丁治疗重症急性胰腺炎的疗效及其可能作用机制.方法 入选86例重症急性胰腺炎患者,根据收治顺序分为观察组和对照组,每组43例.在入院诊断明确后给予常规对症治疗的基础上,观察组采用乌司他丁1×105 U溶于5％葡萄糖溶液或者生理盐水500 mL中,iv gtt,bid,3～5d待病情有所好转后减量至qd.共治疗10d.观察2组临床疗效和症状改善时间,对比2组治疗前后对腹内压及肠黏膜功能指标:D-乳酸、二胺氧化酶(DAO)、免疫球蛋白A(IgA),炎症因子:白细胞介素6(IL-6)、肿瘤坏死因子-α(TNF-α)、IL-8,外周血单核细胞表面Toll样受体4(TLR4)和内毒素受体(CD14).结果 治疗后观察组总有效率93.02％高于对照组72.09％,腹痛、排便症状改善时间短于对照组,中转手术率低于对照组(4.65％ vs 20.93％,P＜0.05);治疗后2组血尿淀粉酶和白细胞计数均较治疗前降低,且观察组低于对照组,差异均有统计学意义(P＜0.05);2组治疗后腹内压、D-乳酸、DAO均较治疗前降低,IgA较治疗前升高,且观察组治疗后腹内压、D-乳酸、DAO分别为(12.21±2.19) mmHg、(6.23±0.78) μg·L-1、(2.56±0.45)U·mL-1低于对照组治疗后,IgA(3.87±0.69)g·L-1高于对照组治疗后,差异均有统计学意义(P＜0.05);两组治疗后炎症因子IL-6、TNF-α、IL-8均较治疗前降低,而观察组治疗后IL-6、TNF-α、IL-8分别为(45.54±6.76)ng·L-1、(6.18±0.98)ng·L-1、(70.31±10.93)ng·L-1,低于对照组治疗后,差异有统计学意义(P＜0.05);治疗后2组外周血单核细胞表面TLR4较治疗前显著降低,观察组治疗后TLR4为(4.47±0.65)％低于对照组治疗后,差异有统计学意义(P＜0.05);2组治疗前后CD14组内和组间比较差异均无统计学意义(P＞0.05).结论 乌司他丁可能通过抑制TLR4表达降低重症急性胰腺炎患者炎症反应达到提高临床疗效,改善临床症状,降低腹内高压和保护肠黏膜功能的作用.“,”AIM To analyze the curative effect of ulinastatin in severe acute pancreatitis,and to explore the possible mechanism.METHODS Totally 86 patients with severe acute pancreatitis were selected,and they were divided into observation group and control group according to the order number,with 43 patients in each group.The patients were given conventional treatment,on this basis,patients in the observation group were treated by ulinastatin (100 000 U ulinastatin was solubled in 500 mL 5％ of glucose solution or saline solution),iv gtt,bid,reduced to qd after 3-5 d when the disease got better.After 10 days,the clinical curative effect,symptoms improvement time,intra-abdominal pressure and index function of intestinal mucosa:D-lactic acid,diamine oxidase (DAO),immunoglobulin A (IgA),inflammation factors:interleukin 6 (IL-6),tumor necrosis factor-α (TNF-α),IL-8,peripheral blood mononuclear cell surface toll-like receptor 4 (TLR4) and endotoxin receptor (CD14) before and after treatment were observed and compared.RESULTS The total effective rate in observation group (93.02％) was higher than that in control group(72.09％) after treatment.The abdominal pain and defecation symptoms improvement time were shorter than those in control group,transfer rate of surgery in observation group was(4.65％)lower than that in control group(20.93 ％).And the difference was statistically significant (P ＜0.05).The blood and urine amylase,white blood cell count were reduced in 2 groups after treatment and the blood and urine amylase,white blood cell count in observation group were lower than control group,and the differences were statistically significant (P ＜ 0.05).The intra-abdominal pressure,D-lactic acid and DAO were reduced in 2 groups after treatment,the IgA was increased;the intra-abdominal pressure,D-lactic acid and DAO in observation group were (12.21 ±2.19) mmHg,(6.23 1 0.78) μg · L-1 and (2.56 ±0.45)U · mL-1 after treatment;they were lower while the IgA (3.87 ± O.69) g · L-1 was higher than the control group after treatment,and the difference was statistically significant (P ＜ 0.05).The IL-6,TNF-α and IL-8 in 2 groups after treatment were reduced,and the IL-6,TNF-α and IL-8 in observation group after treatment were (45.54±6.76) ng · L-1,(6.18 ±0.98) ng · L-1 and (70.31 ± 10.93) ng · L-1 respectively,and they were lower than those in control group after treatment,and the difference was statistically significant (P ＜ 0.05).The peripheral blood mononuclear cell surface TLR4 in 2 groups after treatment reduced significantly.The TLR4 in observation group after treatment was (4.47 ± 0.65) ％,it was lower than that in control group after treatment,and the difference was statistically significant (P ＜0.05).Differences of CD14 between 2 groups before treatment and after treatment were no statistical significance(P ＞ 0.05).CONCLUSION Ulinastatin can reduce inflammatory response in patients with severe acute pancreatitis by inhibiting TLR4 expression to improve the clinical curative effect,improve the clinical symptoms,reduce intra-abdominal pressure and protect the function of intestinal mucosa.