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Original Research Article
Ulinastatin Reduces T Cell Apoptosis in Rats with
Severe Acute Pancreatitis
Chunli Wang, Tao Ma, Xiaolei Zhou, Nan Li and Shengyi
You*
Department of General Surgery, General Hospital of
Tianjin Medical University, Tianjin 300052, China
*For correspondence: Email:
shengyiyou@139.com
Received: 20 October 2013 Revised accepted: 12 December
2013
Tropical Journal of
Pharmaceutical Research, January 2014;
13(1):
47-52
http://dx.doi.org/10.4314/tjpr.v13i1.7
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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