[The mechanisms of thalidomide in treatment of angiodysplasia due to hypoxia].
OBJECTIVE
To investigate the inhibitory effect of thalidomide on angiodysplasia.


METHODS
Excisional intestinal specimens were collected and immunohistochemical examination was carried out. The human umbilical vein endothelial cells were cultured in vitro to exponential phase of growth, divided into six groups and synchronized for 24 hours. They were then stimulated with thalidomide (40 - 100 microg/ml) for 72 hours. MTT assay was used to assess cellular proliferation. ELISA, real-time quantitative PCR and western blot were applied to detect the expression of VEGF/HIF-1alpha of human umbilical vein endothelial cells (HUVEC).


RESULTS
Immunohistochemical analysis of intestinal pathological specimens demonstrated higher expression of VEGF. ELISA showed that the expression of VEGF under hypoxia was obviously higher than that under normoxia [(1199.3 +/- 61.4) ng/L vs (864.7 +/- 41.2) ng/L, P < 0.05]. Real-time quantitative PCR and Western blot discovered that thalidomide inhibited the expression of VEGF/HIF-1alpha of HUVEC (P < 0.05). The effect of thalidomide was dose-dependent.


CONCLUSIONS
Thalidomide can suppress the expression of HIF-1alpha and VEGF in HUVEC in vitro and then inhibit angiodysplasia, which may play a significant role in stopping the rebleeding in patients with recurrent gastrointestinal bleeding.
Chen
Hui-Min
HM
Department of Gastroenterology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute of Digestive Disease, Shanghai 200001, China.
Ge
Zhi-Zheng
ZZ
Liu
Wen-Zhong
WZ
Lu
Hong
H
Xu
Chun-Hong
CH
Fang
Jing-Yuan
JY
Xiao
Shu-Dong
SD
D016888:Angiodysplasia / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D013792:Thalidomide / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D013792:Thalidomide