Abstract：Objective To investigate the effect of ulinastatin (UTI) for early drug intervention on the serum levels of tumor necrosis factor-α (TNF-α), P-selectin, and thrombin-antithrombin complex (TAT) in young rats with sepsis. Methods A total of 120 male rats aged 4 weeks were randomly divided into normal control group, shamoperation group, sepsis group, low-dose UTI group (50 000 U/kg), and high-dose UTI group (200 000 U/kg), with 24 rats in each group. Modified cecal ligation and puncture was performed to establish a rat model of sepsis, and the rats in the low- and high-dose UTI groups were given caudal vein injection of UTI after model establishment. ELISA was used to measure the serum levels of TNF-α, P-selectin, and TAT at 6, 12, and 24 hours after model establishment. Results The sepsis group had significant increases in the serum levels of TNF-α, P-selectin, and TAT at 6 hours, and the serum levels of TNF-α and TAT continued to increase by 24 hours (P < 0.05); P-selectin reached the peak at 12 hours and decreased slightly at 24 hours (P < 0.05). The UTI groups had similar change patterns in the levels of P-selectin and TAT as the sepsis group. The UTI groups had significant increases in the level of TNF-α at 6 hours, but gradually decreased over time. The changes in serum levels of TNF-α, P-selectin, and TAT in the UTI groups were significantly smaller than in the sepsis group (P < 0.05). The high-dose UTI group had significantly smaller changes in serum levels of TNF-α, P-selectin, and TAT than the low-dose UTI group (P < 0.05). Conclusions Early intervention with UTI can significantly improve coagulation function and inhibit the production of TNF-α, P-selectin, and TAT in young rats with sepsis. High-dose UTI has a significantly greater effect than low-dose UTI.
LIU Yun,WU Xing-Heng. Effect of ulinastatin on serum levels of tumor necrosis factor-α, P-selectin, and thrombin-antithrombin complex in young rats with sepsis[J]. CJCP, 2017, 19(2): 237-241.
Fleischmann C,Scherag A,Adhikari NK,et al.Assessment of global incidence and mortality of hospital-treated sepsis.Current estimates and limitations[J].Am J Respir Crit Care Med,2016, 193(3):259-272.
[2]
Singer M,Deutschman CS,Seymour CW,et al.The third international consensus definitions for sepsis and septic shock (sepsis-3)[J].JAMA,2016,315(8):801-810.
[3]
Atal SS,Atal S.Ulinastatin-a newer potential therapeutic option for multiple organ dysfunction syndrome[J].J Basic Clin Physiol Pharmacol,2016,27(2):91-99.
[4]
Uchida M,Abe T,Ono K.The effects of ulinastatin in multiple organ failure:a retrospective observational study in a single center ICU[J].Intensive Care Med Exp,2015,3(Suppl 1):A878.
[5]
Wang FY,Fang B,Qiang XH,et al.The efficacy and immunomodulatory effects of ulinastatin and thymosin α1 for sepsis:a systematic review and Meta-analysis[J].Biomed Res Int,2016,2016:9508493.
[6]
Zhang H,Kovacs-Nolan J,Kodera T,et al.γ-Glutamyl cysteine and γ-glutamyl valine inhibit TNF-α signaling in intestinal epithelial cells and reduce inflammation in a mouse model of colitis via allosteric activation of the calcium-sensing receptor[J].Biochim Biophys Acta,2015,1852(5):792-804.
[7]
Newcomb D,Bolgos G,Green L,et al.Antibiotic treatment influences outcome in murine sepsis:mediators of increased morbidity[J].Shock,1998,10(2):110-117.
[8]
Ruiz S,Vardon-Bounes F,Merlet-Dupuy V,et al.Sepsis modeling in mice:ligation length is a major severity factor in cecal ligation and puncture[J].Intensive Care Med Exp,2016, 4(1):22.
[9]
Vincent JL,Opal SM,Marshall JC,et al.Sepsis definitions:time for change[J].Lancet,2013,381(9868):774-775.
[10]
Shubin NJ,Monaghan SF,Ayala A.Anti-inflammatory mechanisms of sepsis[J].Contrib Microbiol,2011,17:108-124.
[11]
Kutlar A,Embury SH.Cellular adhesion and the endothelium: P-selectin[J].Hematol Oncol Clin North Am,2014,28(2):323- 339.
[12]
Han D,Shang W,Wang G,et al.Ulinastatin-and thymosin α1- based immunomodulatory strategy for sepsis:a meta-analysis[J]. Int Immunopharmacol,2015,29(2):377-382.
[13]
Karnad DR,Bhadade R,Verma PK,et al.Intravenous administration of ulinastatin (human urinary trypsin inhibitor) in severe sepsis:a multicenter randomized controlled study[J]. Intensive Care Med,2014,40(6):830-838.
[14]
Guan L,Liu H,Fu P,et al.The protective effects of trypsin inhibitor on hepatic ischemia-reperfusion injury and liver graft survival[J].Oxid Med Cell Longev,2016,2016:1429835.
[15]
Hao X,Cai G,Hu C.The effect of ulinastatin on sepsis in the rats of adhesion molecules and endothelial function[J].Intensive Care Med Exp,2015,3(Suppl 1):A617.
[16]
Liu G,Li Q.Meta-analysis of xuebijing joint ulinastatin treating sepsis[J].Value Health,2014,17(7):A807.
