Effect of a prostaglandin I(2) analog on the expression of thrombomodulin in liver and spleen endothelial cells after an extensive hepatectomy.
OBJECTIVE
Dysfunction of the remnant liver after a hepatectomy is caused by microthrombus formation due to endothelial cell (EC) damage. This study evaluated the effect of prostaglandin I(2) (PGI(2)) on the expression of thrombomodulin (TM), a marker for the anticoagulant properties of ECs, using cultured human umbilical vein endothelial cells (HUVECs), and using a canine extensive hepatectomy model.


METHODS
The presence of PGI(2) receptors was confirmed on HUVECs by reverse transcription-polymerase chain reaction, and the effect of the PGI(2) analog on TM expression on HUVECs was determined by an enzyme-linked immunosorbent assay. Twenty mongrel dogs were divided into four groups comprising a sham operation, 70% hepatectomy, 84% hepatectomy, and 84% hepatectomy, with the administration of the PGI(2) analog, respectively, and TM expression in the liver, spleen, pancreas, kidney, lung, portal vein, and intestine was determined immunohistochemically.


RESULTS
The TM expression on HUVECs was upregulated by the PGI(2) analog. The TM expression on ECs in the hepatic sinusoids and splenic sinus were markedly decreased after the 84% hepatectomy, but such damage was markedly mitigated following an 84% hepatectomy with administration of the PGI(2) analog.


CONCLUSIONS
An extensive hepatectomy induced severe EC damage not only in the hepatic sinusoids but in the splenic sinuses as well. Prostaglandin I(2) prevented damage to these ECs, suggesting that PGI(2) improves the microcirculation in the remnant liver.
Departments of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, Japan.
Masanobu
M
Usui
Hiroyuki
H
Kato
Naohisa
N
Kuriyama
Yoshinori
Y
Azumi
Masashi
M
Kishiwada
Shugo
S
Mizuno
Hiroyuki
H
Sakurai
Masami
M
Tabata
Tatsuya
T
Hayashi
Koji
K
Suzuki
Shuji
S
Isaji
D000818:Animals; D002478:Cells, Cultured; D004285:Dogs; D042783:Endothelial Cells / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006498:Hepatectomy / Q000379:methods; D006801:Humans; D008099:Liver / Q000098:blood supply / Q000166:cytology*; D008833:Microcirculation; D044006:Receptors, Epoprostenol / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology*; D018180:Thrombomodulin / Q000032:analysis*; D015854:Up-Regulation
D044006:Receptors, Epoprostenol; D018180:Thrombomodulin; C049453:OP 2507; D011464:Epoprostenol
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