[Development of virulent heat-evil-induced thrombosis animal model].
OBJECTIVE
To develop a virulent heat-evil-induced thrombosis animal model, and provide a rational animal model for pathogeny and pathogenesis research of thrombosis-related diseases, anti-thrombosis activity screening and pre-clinical studies of CAHT formula.


METHODS
SD rats were pretreated with carrageenin (Ca) intraperitoneal injection, followed by intravenous injection of endotoxin (LPS from E. coli O111:B4) 50 microg x kg(-1) 16 h later. Thrombosis in rat tails were observed during 12-24 h after injection of LPS. The inflammatory mechanism of this model were investigated by analyzing serum level of TNF-alpha, IL-6, TXB2 and 6-keto-PGF 1alpha, CD11b/CD18 expression of white blood cells (WBC) and P-selectin expression of vessel walls.


RESULTS
In LPS/Ca model group, thrombosis can be clearly observed in the distal part of rat tails after 12-24 h of LPS/Ca treatment. High level of TNF-alpha and IL-6 can be measured in serum. The expression of CD11b/CD18 in WBC and P-selectin in vessel endothelium significantly increased and the number of WBC in peripheral blood markedly decreased shortly after LPS/Ca treatment. The adherence of white blood cells to vessel endothelium which can be seen by microscope mainly contributed to the decrease of WBC. The results indicated that there was obvious inflammation after treatment with LPS/Ca, suggesting that inflammation was the key mechanism for this model.


CONCLUSIONS
This model was developed through treatment of LPS in combination with Ca, of which LPS is considered to be an exotic virulent heat-evil in TCM, while the inflammatory molecules produced in this model, such as TNF-alpha, IL-6, CD11b/CD18 and P-selectin belong to internal virulent heat-evils, so this animal model consists of pathogeny and pathogenesis of virulent heat-evils. virulent heat-evil.
Liang
Ai-Hua
AH
Macau University of Science and Technology, Macau, China. liangaihua@sina.com
Xue
Bao-Yun
BY
Wang
Jin-Hua
JH
Li
Chun-Ying
CY
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002351:Carrageenan / Q000494:pharmacology*; D004195:Disease Models, Animal; D004731:Endotoxins / Q000494:pharmacology*; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000097:blood; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D039481:CD11b Antigen; D018821:CD18 Antigens; D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D015121:6-Ketoprostaglandin F1 alpha; D002351:Carrageenan