【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 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.
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 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.
ObjectiveTo observe the clinical efficacy of ulinastatin combined with low-dose arginine vasopressin in treating severe pulmonary contusion.
MethodSixty patients with severe pulmonary contusion were enrolled in our hospital between April 2012 to June 2014 year. All the patients were randomly divided into three groups. They were respectively defined as a routine treatment group (group A, n=20), an ulinastatin treatment group (group B, n=20), and a combined treatment group (group C, n=20). The respiratory frequency (RR), oxygenation index, partial pressure of carbon dioxide (PaCO2), the change of chest X-ray and the change of serum interleukin-6 (IL-6), IL-8 levels were compared among three groups before and after therapy.
ResultThe respiration frequency(RR) and the concentration of serum IL-6, IL-8 levels were decreased in the group C before and after treatment with statistical differences (P=0.000, 0.000, 0.000). PaO2/FiO2 and PaCO2 were significantly increased in the group C before and after treatment (P=0.000, 0.000). After treatment for 7 d, the respiration frequency (RR) and the concentration of serum IL-6, IL-8 of patients in the group B decreased significantly compared with those in the group A (P=0.000, 0.043, 0.000). While PaO2/FiO2, PaCO 2 and the score of chest X-ray increased significantly in the group B (P=0.010, 0.000, 0.000). Compared with those in the group B, RR and the concentration of serum IL-6, IL-8 of patients in the group C decreased significantly (P=0.000, 0.045, 0.000), while PaO2/FiO2, PaCO2 and the score of chest X-ray increased significantly (P=0.043, 0.010, 0.001).
ConclusionUlinastatin combined with low-dose arginine vasopressin shows obvious effects in the patients with severe pulmonary contusion. And its therapeutical effects are better than that of the other two treatment options.
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.
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 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.
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 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.
