Biliary intervention augments chemotactic reaction and aggravates cholestatic liver injury in rats.
BACKGROUND
Intervention of the biliary system is frequently done in patients with obstructive jaundice and is associated with significant morbidity and mortality. The pathogenesis is unknown.


METHODS
A rat model of bile duct ligation (BDL) for 2 weeks was established in which biliary intervention was feasible by injection of normal saline through an indwelling catheter in the bile ducts. Plasma levels of C-C chemokine MCP-1 and C-X-C chemokine MIP-2 were measured by using ELISA. Blood monocytes, Kupffer cells, and neutrophils in the liver were characterized with antibodies to ED1, ED2, and myeloperoxidase (MPO). Lipid peroxidation was measured by malondialdehyde contents and apoptosis by TUNEL stain of the liver.


RESULTS
Biliary intervention resulted in an increase of plasma MCP-1 and MIP-2 proteins by 1 h, which declined to normal level by 3 h in both sham and BDL rats. The levels in BDL rats were significantly higher than in sham at most points. There was a transient increase of ED1- and ED2-positive cells and MPO-staining cells in sham rat liver by 1 h after intervention. ED2-positive cells increased significantly by 1 h, while ED1- and MPO-positive cells decreased, yet insignificantly after intervention in BDL rats. The cell counts in BDL were constantly higher than in sham. Malondialdehyde increased precipitously in BDL by 3 h and was significantly higher than in sham throughout the study period. Parenchymal liver injury, manifested by elevated ALT, as well as apoptosis and necrosis of liver cells, was significantly increased in BDL rats, but not in sham rats.


CONCLUSIONS
Biliary intervention augments chemokine expression, precipitates lipid peroxidation, and aggravates liver injury in cholestatic rats.
Chuang
Jiin-Haur
JH
Graduate Institute of Clinical Medical Sciences, Chang Gung University, and Chang Gung memorial Hospital, 123 Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung Hsien, Taiwan. jhchuang@adm.cgmh.org.tw
Chang
Nyuk-Kong
NK
Huang
Chao-Cheng
CC
Lo
Sing Kai
SK
Wang
Hsiu-Chuan
HC
Chen
Ching-Mei
CM
Wu
Chia-Ling
CL
Chou
Ming-Huei
MH
Lin
Tsu-Kung
TK
D000818:Animals; D001652:Bile Ducts; D002408:Catheters, Indwelling; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D019743:Chemokines, CXC / Q000378:metabolism; D002633:Chemotaxis; D002779:Cholestasis / Q000473:pathology* / Q000503:physiopathology*; D053331:Ectodysplasins; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008026:Ligation; D008099:Liver / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000008:administration & dosage*
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; C513296:Cxcl2 protein, rat; D053331:Ectodysplasins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D020033:Protein Isoforms; D011506:Proteins; D012965:Sodium Chloride; D008315:Malondialdehyde; D009195:Peroxidase