Objective To investigate the effects of ulinastatin on Treg/Th17 and immune status in patients with severe sepsis.Methods A total of 80 patients with severe sepsis, who were hospitalized in ICU during October 2011 to July 2012, were randomly divided into a routine group and a ulinastatin group. The patients in the ulinastatin group were intravenously administered 30mg ulinastatin three times per day for 5 days in addition to routine bundle treatment. The expression of Treg, Th17 and HLA-DR were detected on the first day in ICU and 5 days after treatment. 20 healthy individuals served as controls. Results Compared with the control group, the severe sepsis group had overexpression of Treg and Th17 ( P lt;0. 01) , higher ratio of Treg/Th17( P lt;0. 01) , and decreased HLA-DR expression of CD14 monocyte ( P lt; 0. 01) . In the severe sepsis patients, ulinastatin injection reduced the abnormal expression of Treg and Th17 ( P lt; 0. 01) , decreased the ratio of Treg/Th17( P lt; 0. 01) , and improved the expression of HLA-DR ( P lt; 0. 01) more effectively compared with the routine treatment. Ulinastatin also lowered 28-day mortality of the patients with sepsis, but the difference between the ulinastatin group and the routine group was not significant. Conclusions In severe sepsis patients, there were abnormal overexpression of Treg and Th17, imbalance of Treg/Th17, and underexpression of HLA-DR which imply an immune suppression. Ulinastatin can decrease the expression of Treg and Th17, inverses the ratio of Treg/Th17, and improve the expression of HLA-DR, so as to improve the prognosis of severe sepsis 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.
Objective To evaluate the effectiveness and safety of Octreotide combined with Ulinastatin for treating acute pancreatitis in China. Methods The databases such as CBM, VIP, CNKI and WanFang Data were searched to collect randomized controlled trials (RCTs) from the date of their establishment to February 2011, and the relevant references of the included studies were also retrieved. Studie were screened, data were extracted, and the methodological quality was assessed by two reviewers independently. Meta-analyses were conducted by using RevMan 5.1 software. Results A total of 12 studies involving 1 023 participants were included. The results showed that compared with the group of routine therapies and the group of single administration of either Octreotide or Ulinastatin, the experimental group of Octreotide combined with Ulinastatin was superior in the following aspects with singnificant differences: the total effective rate (RR= 0.34, 95%CI 0.23 to 0.52), the remission time of abdominal pain and distention (SMD= –0.89, 95%CI –1.09 to –0.70), the remission time of signs of abdominal tenderness (SMD= –0.95, 95%CI –1.48 to –0.42), the average length of hospital stay (SMD= –1.10, 95%CI –1.58 to –0.63), the time for blood amylase returning to normal (SMD= –1.14, 95%CI –2.10 to –0.17) and the positive cases at the end of treatment (RR= 0.20, 95%CI 0.08 to 0.51), the time for urine amylase returning to normal (SMD= –0.86, 95%CI –1.04 to –0.68) and the positive cases at the end of treatment (RR= 0.27, 95%CI 0.12 to 0.63), the IL-6 level at the end of treatment (SMD= –2.25, 95%CI –4.39 to –0.11), the incidence rate of complications (RR= 0.39, 95%CI 0.28 to 0.55), the required rate of operation (RR= 0.41, 95%CI 0.24 to 0.69), and the mortality (RR= 0.43, 95%CI 0.29 to 0.64). But the experimental group showed a little longer time for blood calcium returning to normal without statistic difference (MD =0.15, 95%CI 0.05 to 0.26).Conclusion According to the domestic evidence, Octreotide combined with Ulinastatin for treating acute pancreatitis is superior to both the routine therapies and the singe administration of either Octreotide or Ulinastatin. It provides a new and prospective therapeutic method for AP. However, this conclusion has to be further verified by high quality, large scale and double blinded RCTs.
【摘要】 目的 探讨严重腹腔感染合并呼吸循环功能障碍的有效治疗方法。方法 选择2004 年10 月至2006 年5 月期间我院ICU 收治的严重腹腔感染合并呼吸循环功能障碍患者42 例,其中治疗组( n = 22) 应用乌司他丁和生长激素联合治疗方案,对照组( n = 20) 应用常规治疗。比较2 组病例的临床病死率,并对2 组病例的ICU 住院时间及呼吸支持时间、循环支持时间的差异进行分析。结果 治疗组与对照组的临床病死率(22. 7 % vs35. 0 %) 差异无统计学意义( Pgt; 0. 05) ,而治疗组较对照组ICU 住院时间〔(12. 1 ±4. 2) d vs (18. 8 ±3. 6) d〕、呼吸支持时间〔(10. 1 ±3. 1) d vs (15. 4 ±4. 4) d〕及循环支持时间〔(5. 6 ±1. 8) d vs (11. 3 ±2. 1) d〕明显减少( P lt;0. 05) 。结论 乌司他丁和生长激素联合使用可以改善严重腹腔感染合并呼吸循环功能障碍的治疗效果。
Objective To investigate the change of the platelet parameter and to study the therapeutic effects of ulinastatin (UTI) on platelet parameter in patients with acute pancreatitis (AP). Methods The data of 80 patients with AP were analyzed retrospectively. All patients were divided into two groups: mild acute pancreatitis (MAP, n=43) and severe acute pancreatitis (SAP, n=37). Thirty people who took the medical examination and whose results were normal were included as control group. The autocytometer was used to test PLT, PCT, MPV and PDW in different periods of SAP. Results On admission, there were no significant differences of PLT, PCT between MAP group and control group (Pgt;0.05), but MPV and PDW in MAP group were higher than those of control group (plt;0.05). Compared with MAP group, PLT and PCT decreased markedly in SAP group (plt;0.01), while MPV and PDW significantly increased (plt;0.05). After 1-week treatment of UTI, PLT and PCT in MAP group didn’t change dramatically, while MPV and PDW decreased significantly (plt;0.05). While in SAP group, PLT and PCT increased significantly (plt;0.05, plt;0.01), and MPV and PDW decreased significantly (plt;0.01, plt;0.05). Compared with conventional treatment， PLT and PCT in MAP group increased significantly in UTI treatment group （plt;0.05）, but there was no statistical difference in terms of MPV and PDW （Pgt;0.05）. However, SAP group showed significant increase of PLT and PCT （plt;0.01， plt;0.05） and decrease of MPV and PDW in UTI treatment group compared with patients treated by conventional methods （plt;0.01）. Conclusion The platelet parameter changes in patients with acute pancreatitis, and the changes of SAP patients are more mark than those of MAP patients. UTI can significantly increase PLT and PCT, and significantly decrease the activity of the platelet. Therefore, UTI may take a role in the treatment and prevention for SAP.
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.
【Abstract】Objective To investigate therapeutic effect and mechanism of hyperbaric oxygen and ulinastatin respectively or combinatively used to treat acute necrotizing pancreatitis (ANP). Methods One hundred and twenty SD rats were divided into 6 groups randomly: group of normal control, group receiving sham operation, group of untreated acute necrotizing pancreatitis (ANP group), group of acute necrotizing pancreatitis treated with hyperbaric oxygen (HBO group), group of acute necrotizing pancreatitis treated with ulinastatin (ULT group), and group of acute necrotizing pancreatitis treated with combined hyperbaric oxygen and ulinastatin (HBO+ULT group). The rat model of acute necrotizing pancreatitis was established according to Aho HJ et al. Concentrations of amylase, TNFα, TXB2 and 6ketoPGF1α in blood were measured through ELISA or radioimmunoassay. Changes of pancreatic histopathology were investigated. SPSS 10.0 was used in statistical analysis. Results The concentrations of amylase, TNFα, TXB2 in the ANPtreated groups were significantly lower than those of ANP group (P＜0.01) except for 6ketoPGF1α and the levels of amylase and TNFα of HBO group were strikingly higher than those in HBO+ULT group. Only the level of AMS was significantly different between ULT group and HBO+ULT group (P＜0.01). Pancreas histopathological scores(HS) and CD8 counts of ANP group were significantly higher than those the other three group, but CD4 counts and CD4/CD8 ratio were on the contrary (P＜0.05). HS of HBO and ULT were strikingly higher than those of HBO+ULT (P＜0.05).Conclusion ①Hyperbaric oxygen or ulinastatin can effectively decrease the blood levels of enzymes and cytokines and improve the pancreatic immunity. ②Hyperbaric oxygen in combination with ulinastatin are more effective than either of them in the treatment of ANP.
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.