Effects of large dose of dexamethasone on inflammatory mediators and pancreatic cell apoptosis of rats with severe acute pancreatitis.
OBJECTIVE
To investigate the influence of high dose of dexamethasone on inflammatory mediators and apoptosis of rats with severe acute pancreatitis (SAP).


METHODS
SAP rats were randomly assigned to the model group and treatment group while the normal rats were assigned to the sham operation group. The mortality, ascite volumes, ascites/body weight ratio and pancreas pathological changes of all rats were observed at 3, 6 and 12 h after operation. Their contents of amylase and endotoxin in plasma and contents of tumor necrosis factor (TNF-alpha), phospholipase A(2) (PLA(2)) and IL-6 in serum were also determined. The microarray sections of their pancreatic tissues were prepared, terminal transferase dUTP nick end labeling (TUNEL) staining was performed and apoptotic indexes were calculated.


RESULTS
There was no marked difference between treatment group and model group in survival. The contents of amylase and endotoxin in plasma and contents of TNF-alpha, PLA(2) and IL-6 in serum, ascite volumes, ascites/body weight ratio and pancreas pathological scores were all lower in treatment group than in model group to different extents at different time points [P < 0.05, 58.3 (26.4) ng/L vs 77.535 (42.157) ng/L in TNF-alpha content, 8.00 (2.00) points vs 9.00 (2.00) points in pathological score of pancreas respectively; P < 0.01, 0.042 (0.018) EU/mL vs 0.056 (0.0195) EU/mL in endotoxin content, 7791 (1863) U/L vs 9195 (1298) U/L in plasma amylase content, 1.53 (0.79) vs 2.38 (1.10) in ascites/body weight ratio, 8.00 (1.00) points vs 11.00 (1.50) points in pathological score of pancreas; P < 0.001, 3.36 (1.56) ng/L vs 5.65 (1.08) ng/L in IL-6 content, 4.50 (2.00) vs 7.20 (2.00), 4.20 (1.60) vs 6.40 (2.30), 3.40 (2.70) vs 7.90 (1.70) in ascite volumes, respectively]. The apoptotic indexes of pancreas head and pancreas tail were all higher in treatment group than in model group at 6 h [P < 0.01, 0.00 (2.00)% vs 0.00 (0.00)%, 0.20 (1.80) vs 0.00 (0.00) in apoptosis indexes, respectively].


CONCLUSIONS
The mechanism of dexamethasone treatment in acute pancreatitis is related to its inhibition of inflammatory mediator generation and induction of pancreatic acinar cell apoptosis.
Zhang
Xi-Ping
XP
Department of General Surgery, Hangzhou First People's Hospital, 261 Huansha Road, Hangzhou 310006, Zhejiang Province, China. zxp99688@vip.163.com
Chen
Li
L
Hu
Qi-Fang
QF
Tian
Hua
H
Xu
Ru-Jun
RJ
Wang
Zhi-Wei
ZW
Wang
Ke-Yi
KY
Cheng
Qi-Hui
QH
Yan
Wei
W
Li
Yun
Y
Li
Qing-Yu
QY
He
Qing
Q
Wang
Fei
F
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001201:Ascites / Q000473:pathology / Q000517:prevention & control; D001835:Body Weight / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000097:blood; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000097:blood / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D054467:Phospholipases A2 / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013997:Time Factors; D046888:Tissue Array Analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000893:Anti-Inflammatory Agents; D004731:Endotoxins; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D054467:Phospholipases A2; D000681:Amylases