Thalidomide decreases intrahepatic resistance in cirrhotic rats.
Increased intrahepatic resistance (IHR) within cirrhotic liver is caused by increased endotoxemia, cytokines tumor necrosis factor-alpha (TNF-alpha), vasoconstrictor thromboxane A(2) (TXA(2)), and disrupted microvasculatures. We evaluated the effects of thalidomide-related inhibition of TNF-alpha upon the hepatic microcirculation of cirrhosis in rats. Portal venous pressure (PVP), hepatic TNF-alpha, expression of thromboxane synthase (TXS), and leukocyte common antigen (LCA) were measured in bile-duct-ligated (BDL) rats receiving 1 month of thalidomide (BDL-thalido rats). Portal perfusion pressure (PPP), IHR, and hepatic TXA(2) production were measured in the isolated liver perfusion system. Intravital microscopy was used to examine hepatic microvascular disruptions. In BDL-thalido rats, PVP, PPP, IHR, hepatic TXA(2) and TNF-alpha, hydroxyproline content, expression of TXS and LCA, and LPS-induced leukocyte recruitment were significantly decreased. Conversely, hepatic microvascular density and perfused sinusoids were significantly increased. Thalidomide decreased PVP and IHR by reducing hepatic TXA(2) and improving hepatic microvascular disruptions in rats with biliary cirrhosis.
Yang
Ying-Ying
YY
Division of General Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Huang
Yi-Tsau
YT
Lin
Han-Chieh
HC
Lee
Fa-Yauh
FY
Lee
Kuei-Chuan
KC
Chau
Ga-Yang
GY
Loong
Che-Chuan
CC
Lai
Chiung-Ru
CR
Lee
Shou-Dong
SD
D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008099:Liver / Q000098:blood supply / Q000187:drug effects*; D008105:Liver Cirrhosis, Biliary / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D011169:Portal Vein / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013792:Thalidomide / Q000494:pharmacology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects*; D014690:Venous Pressure / Q000187:drug effects
D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D017493:Leukocyte Common Antigens; D013930:Thromboxane-A Synthase