Ulinastatin Reduces T Cell Apoptosis in Rats with Severe Acute Pancreatitis
Purpose: To investigate the immunoregulative effects of ulinastatin (UTI) on T lymphocytes apoptosis in rats with severe acute pancreatitis (SAP) and to elucidate its underlying molecular mechanism.
Methods: Thirty six Wistar rats were randomly divided into 3 groups (n =12): sham, SAP model and UTI-treated group. SAP model was established by intrapancreatobiliary duct injection of 5% sodium taurocholate. A bolus of 10000 U/kg UTI was intravenously injected after SAP establishment. T cell apoptosis was determined by Annexin-V/PI double-staining. Oxidative stress was evaluated by examining changes in the levels of reactive oxygen species (ROS). Total superoxide dismutase (SOD) in serum was tested by hydroxylamine colorimetric assay, and malondialdehyde levels were examined by thiobarbituric acid assay. Mitochondrial function was evaluated by analyzing mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (MPTP).
Results: We found CD4 + T cells (32.10±2.87% vs. 45.22±4.38%, P<0.01) and CD4 +/CD8 + T cells in SAP rats significantly decreased compared with sham group (1.15±0.12 vs. 2.23±0.12%, P<0.01), while the percent of the apoptotic CD4 + and (17.70±2.10 vs. 3.82±0.50%, P<0.01) CD8
+ T lymphocytes was highly increased (2.78±0.45 vs. 1.97±0.36%, P<0.01 compared with sham group). After UTI treatment, the apoptosis of CD4
+ T lymphocytes significantly decreased compared with SAP group (8.58±1.09 vs. 17.70±2.10%, P<0.01), while the percent of CD4 + T and CD4 +/CD8 + lymphocytes significantly enhanced (P<0.01). ROS (mean fluorescence intensity): 5107±430 vs. 12904±840, P<0.01) and MDA levels
(4.41±0.32 vs. 7.25±0.57nmol/ml, P<0.01) in serum in UTI-treated group were decreased compared with SAP group. SOD activity was enhanced after UTI treatment (59.72±5.45 vs. 48.32±3.81nmol/ml, P<0.01). Mitochondrial function assays showed that MMP (17.30±1.60 vs. 46.94±3.49%, P<0.01) and MPT (30.14±2.46 vs. 51.31±3.23%, P<0.01) were inhibited by UTI.
Conclusion: UTI reduces T lymphocytes apoptosis and improves immunological function in SAP rats, possibly via enhancing the scavenging capacity of oxygen free radical and attenuating the influence of oxidative stress.
Key words: Ulinastatin, T cell, Apoptosis, Severe acute pancreatitis, Mitochondrion
Submission of a manuscript to this journal is a representation that the manuscript has not been published previously and is not under consideration for publication elsewhere.
All authors named in each manuscript would be required to sign a form (to be supplied by the Editor) so that they may retain their copyright in the article but to assign to us (the Publishers) and its licensees in perpetuity, in all forms, formats and media (whether known or created in the future) to (i) publish, reproduce, distribute, display and store the contribution, (ii) translate the contribution into other languages, create adaptations, reprints, include within collections and create summaries, extracts and/or abstracts of the contribution, (iii) create any other derivative works(s) based on the contribution, (iv) to exploit all subsidiary rights in the contribution, (v) the inclusion of electronic links from the contribution to third party material where-ever it may be located, and (vi) license any thrid party to do any or all of the above.