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Ulinastatin Reduces T Cell Apoptosis in Rats with Severe Acute Pancreatitis Wang, Chunli; Ma, Tao; Zhou, Xiaolei; Li, Nan & You, Shengyi Abstract 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. Keywords Ulinastatin; T cell; Apoptosis; Severe acute pancreatitis; Mitochondrion

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