Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Ulinastatin Reduces T Cell Apoptosis in Rats with Severe Acute Pancreatitis

Chunli Wang, Tao Ma, Xiaolei Zhou, Nan Li, Shengyi You

Department of General Surgery, General Hospital of Tianjin Medical University, Tianjin 300052, China;

For correspondence:- Shengyi You Email: shengyiyou@139.com

Received: 20 October 2013 Accepted: 12 December 2013 Published: 25 January 2014

Citation: Wang C, Ma T, Zhou X, Li N, You S. Ulinastatin Reduces T Cell Apoptosis in Rats with Severe Acute Pancreatitis. Trop J Pharm Res 2014; 13(1):47-52 doi: 10.4314/tjpr.v13i1.7

© 2014 The authors.
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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