Hyperlipidemia intensifies cerulein-induced acute pancreatitis associated with activation of protein kinase C in rats.
OBJECTIVE
To investigate the effects of hyperlipidemia on acute pancreatitis (AP) and the possible mechanisms.


METHODS
Rat models of hyperlipidemia and AP were established by Triton WR1339 and cerulein respectively. Human albumin was used to treat AP complicated by hyperlipidemia. In each group, we compared the histological score, volume of ascites, ratio of pancreatic wet/dry weight, serum amylase (AMY) and pancreatic acinar cell apoptosis. The level of protein kinase C (PKC) membrane translocation in pancreatic tissue was detected by Western blot.


RESULTS
In the hyperlipidemia model established by Triton WR1339, triglyceride (TG) increased remarkably and reached its peak 6 h after injection, and most rats developed mild acute pancreatitis. Histological score, volume of ascites, ratio of wet/dry weight and serum AMY in AP animals with hyperlipidemia were obviously higher than those in AP animals (P < 0.05) and decreased after albumin therapy but not significantly (P > 0.05). Apoptotic cells detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) increased in AP animals with hyperlipidemia and did not change distinctly after albumin therapy. PKC membrane translocation level increased in AP animals with hyperlipidemia and decreased remarkably after albumin therapy (P < 0.05).


CONCLUSIONS
Hyperlipidemia may induce AP or intensify pancreatic injury. Albumin therapy can not alleviate pancreatic lesion effectively. PKC activation may be one mechanism by which AP is intensified by hyperlipidemia.
Wang
Ya-Jun
YJ
Department of General Surgery, Xuanwu Hospital of Capital University of Medical Sciences, 45 Changchun Street, Beijing 100053, China. wyjwmj@yahoo.com.cn
Sun
Jia-Bang
JB
Li
Fei
F
Zhang
Shu-Wen
SW
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001201:Ascites / Q000473:pathology; D002108:Ceruletide / Q000009:adverse effects* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006949:Hyperlipidemias / Q000097:blood / Q000503:physiopathology*; D020287:In Situ Nick-End Labeling; D008055:Lipids / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D011092:Polyethylene Glycols / Q000009:adverse effects; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D008055:Lipids; D011092:Polyethylene Glycols; D002108:Ceruletide; D011493:Protein Kinase C; D000681:Amylases; C016811:tyloxapol