Objective To explore the effects of ulinastatin (UTI) on renal apoptosis and expression of bcl-2 in rats with severe acute pancreatitis (SAP). Methods Sixty rats weighing 250-300 g were randomized divided into 3 groups: pseudo-operation group (SO group, n=20), SAP group (n=20) and UTI treated group (UTI group, n=20). The model of SAP was established by retrograde injection of 5% sodium taurocholate solution into the biliopancreatic duct in the rats. Serum Cr and BUN were determined. The left kidneys were resected for light and electronic microscopic study. Renal cell apoptosis was determined by TUNEL. Expression of bcl-2 was detected by immunohistochemical staining of SABC. Results Serum Cr, BUN, renal cell apoptotic index and bcl-2 expression were markedly increased in SAP group compared with SO group （P＜0.05， P＜0.01）, Renal tissue injuries were aggravated in SAP group under light and electronic microscopic study as well. In UTI group, serum Cr, BUN and renal cell apoptotic index were decreased significantly while the expression of bcl-2 increased remarkably and renal tissue injuries relieved compared with SAP group （P＜0.05）. Positive correlations were found between the renal cell apoptotic index and BUN as well as Cr (r=0.807, P＜0.05; r=0.812, P＜0.05). Conclusion The protective effect of UTI on SAP renal injury is probably through increasing bcl-2 expression and decreasing apoptosis.
Objective To investigate whether protease inhibitor (ulinastatin, UTI) can protect liver from ischemiareperfusion injury in hepatocellular carcinoma (HCC) patients undergoing hepatectomy after hepatic inflow occlusion. Methods A prospective randomized control study was designed. Thirtyone HCC patients undergoing hepatectomy after hepatic inflow blood occlusion were randomly divided into the following two groups. UTI group (n=16)， 1×105 units of ulinastatin was given intravenously in operation, then the dosage was continuously used twice a day up to 5 days postoperatively. Control group (n=15), the patients received other liver protective drugs. Liver function, plasma C-reactive protein (CRP) and cortisol level were compared between these two groups. Results The postoperative liver function of the UTI group was significantly improved compared with the control group. For example, on the third postoperative day the aspartate transaminase (AST), alanine transaminase (ALT) and total bilirubin level in the UTI group were significantly lower than those in the control group, respectively (P＜0.05). On the first postoperative day, the plasma CRP concentration in the UTI group was significantly lower than that in the control group(P＜0.01). The plasma cortisol level in the control group markedly increased compared with the level before operation(P=0.046). However, there was no significant difference in the UTI group between before and after operation. Conclusion Ulinastatin can effectively protect liver from ischemia/reperfusion injury in HCC patients undergoing hepatectomy performed after hepatic inflow occlusion. Also, it can relieve the surgical stress for patients.
ObjectiveTo explore the effects of urinastatin(UTI) on microcirculation of extrapancreatic organs in rats with acute necrotizing pancreatitis(ANP). Methods A total of 48 rats were randomized into control group, ANP group and UTI group. The model of ANP was established by uniform injection of 5% sodium taurocholate solution under pancreatic capsule, only injection of normal saline in control group. Then the rats of UTI group were injected with UTI through the femoral vein, the rats of ANP group and control group were injected with normal saline. The blood flow of lung, kidney and distal small intestine was measured by radioactive biomicrosphere technique at 2 h and 6 h after ANP.ResultsCompared with the control group, the blood flow of lung, kidney and intestine was decreased significantly in the ANP group at the 2 h and 6 h after ANP （P＜0.05）, compared with the ANP group, the blood flow was increased significantly in UTI group （P＜0.05）. ConclusionMicrocirculation disorder is an important factor of the extrapancreatic organ damage in ANP, and UTI plays a protective role against microcirculation disorder of the extrapancreatic organ in ANP.
目的 观察乌司他丁对多发伤患者的治疗作用和对肝、肾功能的保护作用。方法 46例多发伤患者随机分为治疗组（23例）和对照组（23例）。治疗组从入院第1天开始，每天静脉点滴乌司他丁10万单位+生理盐水100 ml，每8 h 1次，连续用药6 d，观察患者的临床指标判断疗效，并在入院时以及术后第1、3、5、7天检测谷丙转氨酶（ALT）、谷草转氨酶（AST）、血尿素氮（BUN）、血肌酐（Scr）、血浆肿瘤坏死因子-α（TNF-α）、白细胞介素-2（IL-2）、白细胞介素-6（IL-6）以及白细胞介素-8（IL-8）含量的变化。结果 多发伤患者治疗组平均住院时间及平均住ICU时间均低于对照组，差异有显著性意义（P＜0.05）； 治疗组术后血浆ALT、AST、BUN及Scr浓度均明显低于对照组（P＜0.05）； 治疗组术后血浆TNF-α水平逐渐降低，对照组维持在较高水平； IL-2、IL-6及IL-8水平低于对照组（P＜0.05）。结论 乌司他丁对多发伤有治疗作用，并能减轻机体的全身炎症反应程度，有保护和改善肝、肾功能的作用。
Objective To investigate the possible role of ulinastatin(UTI) in f lipopolysacccharide (LPS)-induced acute lung injury(ALI).Methods Thirty male SD rats were randomly divided into three groups，ie.a normal control group，a LPS group and a LPS plus UTI group.The rats were injected with 1 mL of normal saline via caudal vein in the control group，with LPS 5 mg/kg via caudal vein in the LPS group，and with UTI 100000 U/kg shortly after injection with LPS in the LPS plus UTI group.The rats were sacrificed 4 h after the injection.Lung wet/dry weight ratio was measured.IL-18 level in serum and lung tissue was determined by ELISA and the expression of NF-κB in lung tissue was determined by immunohistochemistry.Pathological changes of rats’ lung were observed by optical and electron microscope.Results Compared with the control group，IL-18 level in serum and NF-κB expression in lung tissue were significantly higher in the LPS group(Plt;0.01).The IL-8 level was somewhat elevated in the LPS+UTI group but with no significant difference from that in control group was found (Pgt;0.05).The lung inflammation in the LPS+UTI group was milder than that in the LPS rats.Conclusion UTI can alleviate LPS-induced inflammatory reaction and lung injury in rat model.
Objective To study the protective effects of ulinastatin( UTI) on lung function after cardiopulmonary bypass( CPB) . Methods 42 Patients, ASA score Ⅱ ～Ⅲ, scheduled for elective cardiac valve replacement, were randomly allocated into three groups, ie. a control group, a low dose UTI group( UTI 8000U/kg) , and a high dose UTI group( UTI 12 000 U/kg) . Inspiratory pressure( PIP) , Plateau pressure ( Pplat) , alveolar-arterial oxygen pressure difference ( AaDO2 ) , static lung compliance ( Cs) and dynamic lung compliance ( Cd) were recorded before operation ( T1 ) and at 1 hour ( T2 ) , 4 hours ( T3 ) , 24 hours ( T4 ) after CPB termination. Results Compared with pre-CPB, postoperative PIP, Pplat and AaDO2 increased, and Cs and Cd decreased significantly in the control group( all P lt; 0. 05) . Compared with the control group at T2 ～T3 , postoperative PIP, Pplat, AaDO2 were significantly lower( P lt;0. 05) , and Cs and Cd were significantly higher in the two UTI groups( P lt;0. 05) . Compared with the low dose UTI group at T2 ～T3 , the PIP, Pplat and AaDO2 were significantly reduced( P lt;0. 05) , and the Cs and Cd were significantly increased in the high dose UTI group( P lt; 0. 05) . Conclusion UTI can alleviate lung injury and improve lung function during valve replacement surgery with CPB in a dose dependent manner.
Objective To investigate the protective effects of ulinastatin on acute lung injury ( ALI)induced by seawater drowning in rats. Methods Thirty male SD rats were randomly divided into three groups, ie. a control group, a model group, and an ulinastatin treatment group. The rats in the model group and the ulinastatin treatment group received intratracheal artificial seawater ( 4 mL/kg) instillation. Then the ulinastatin treatment group received ulinastatin ( 100 000 U/kg) injection after infusion of seawater while the model group received an injection of same amount of saline. The rats were sacrificed at 4 hours after instillation. The pathological changes of lung were evaluated by hematoxylin-eosin stain under light microscope. Lung wet/dry weight ratios were measured to assess the level of pulmonary edema.Concentrations of tumor necrosis factor ( TNF) -α, interleukin ( IL) -1β, IL-6, and IL-10 in bronchoalveolar lavage fluid ( BALF) were detected by enzyme-linked immunosorbent assay ( ELISA) . The myeloperoxidase activity in lung tissue homogenates were measured by colorimetric method. Results Ulinastatin treatmentsignificantly relieved the decline of PaO2 and lung pathological changes, inhibited myeloperoxidase activity,and reduced lung wet/dry weight ratios. Ulinastatin also inhibited the release of TNF-α, IL-1β, and IL-6,whereas increased the expression of IL-10 simultaneously. Conclusion Ulinastatin attenuates seawater induced ALI, which may be related to its inhibitory effects on inflammation reaction through regulating cytokine secretion.
Objective To investigate the protective mechanism of ulinastatin（UTI） in pulmonary microvascular endothelial cells （PMVECs） attacked by serum from the patients with severe sepsis. Methods PMVECs were cultured in vitro and randomly divided into 4 groups，ie. a normal group （culture medium with 10% fetal bovine serum，group N），a health group （culture medium with 10% healthy human serum，group H），a patient group （culture medium with 10% human septic shock serum，group S），and a ulinastatin group （culture medium with 1000 U/mL UTI and 10% human septic shock serum，group U）. The proliferation activity of PMVECs was measured by MTT expressed by optical density （OD）. The concentration of TNF-α in supernatant of culture medium was examined by ELISA at 0，1，2，4，6 hours. The expression of NF-κB was examined by immunohistochemistry at 1 hour. Results Compared with group N，the cell proliferation activity of group S decreased significantly，and the cell proliferation activity of group U decreased slightly at each time poi nt. Compared with group N，the cell proliferation activity of group S and group U at 1，4，6 hours were significant different （Plt;0.05 ）. Compared with group S，the cell proliferation activity of group U at 1，2，6 hours increased significantly （Plt;0.05）. Obviously positive expression of NF-κB in PMVECs could be seen in group S，a little positive expression in group S，and no expression in group N and group H. Compared with group N，the TNF-α levels of group S and group U increased significantly at each time point with significant differences （Plt;0.01）. Compared with group S，the TNF-α levels were significantly reduced at each time point in group U （Plt;0.01）. Conclusions UTI can reduce the release of TNF-α by inhibiting NF-κB activation，thus reduce PMVECs injury attacked by serum from severe sepsis patients.
Abstract: Objective To evaluate the protective effects of Ulinastatin on the peri-operative liver and renal function in patients undergoing cardiac surgery for tetralogy of Fallot (TO F). Methods Thirty-eight patients with TOF were divided into Ulinastatin group and control group according to admission sequence, 19 cases in each group.For Ulinastatin group, intravenous Ulinastatin was given with a dosage of 10 000U /kg at 1h before operation, 1h and 24 h after operation. For control group, no Ulinastatin was given. 10 ml fresh urine and 2 ml blood samples were collected before operation, and postoperative 1h, 10h, 24h, 48h and 72h, respect ively. The liver and renal functions were measured. Fluid intake, urine output, chest drainage, dosage of furosemide, durations of mechanical ventilation and intensive care unit ( ICU ) stay were recorded. Results Neither arrhythmia nor low cardiac output syndrome occurred for both groups. No peri-operative death. Compared with control group, dose of furosemide, period of mechanical ventilation were lower, while urine output was higher in Ulinastat in group; the aberrant climax value of urine pro tein and N-acetylglucosam inidase (NAG) were lower in Ulinastatin group (10h post-operat ively, urinem icroalbum in: 65. 2 ± 58. 3mg/L vs. 71. 8 ±58. 9mg/L ; urine transferrin: 5. 8 ± 3. 6mg/L vs. 7. 4 ± 5. 4mg/L ; urine immunoglobulin G: 26. 9±20. 3mg/L vs. 31. 3±23. 3mg/L ; 1h post-operat ively; urine NAG: 61. 4±81. 6U /L vs. 76.1±48. 5 U /L ; P lt; 0. 05) and maintained in shorter period (P lt; 0. 05) , it returned to baseline value at 48h and 72 h post-operatively. The value of alanine aminotransferase (ALT) significantly increased post-operatively at every time points in control group (P lt; 0. 01) , w hile no obvious change in Ulinastat in group (P gt; 0. 05). The increased value of aspartate aminotransferase (AST ) in Ulinastatin group was significantly lower than that in control group (10h post-operat ively: 144. 4±20. 8U /L vs. 202. 7±74. 1U /L ; P lt; 0. 01). The value of AST returned to baseline value at 48h and 72h post-operat ively. Conclusion U linastatin is an effect ive strategy for protecting peri-operat ive liver and renal function of the patients with tetralogy of Fallot and the clinical application of Ulinastatin is safe and effective.