Hyperbaric oxygen preconditioning promotes angiogenesis in rat liver after partial hepatectomy.
Hyperbaric oxygen preconditioning (HBO-PC) increases the level of HIF-1alpha (hypoxia inducible factor-1alpha) and its target gene VEGF (vascular endothelial growth factor) which is involved in angiogenesis. Liver regeneration is an angiogenesis-dependent process. We hypothesized that HIF-1alpha and VEGF mediated the angiogenesis effect of HBO-PC on regenerating rat liver. Male Sprague Dawley rats received HBO-PC followed by 70% partial hepatectomy. Proliferation of hepatocytes and endothelial cells was evaluated by BrdU (bromodeoxyuridine) staining. Microvascular density was assessed by immunohistochemistry. mRNA expression of HIF-1alpha was assessed by quantitative RT-PCR and protein levels of HIF-1alpha and VEGF were assessed by western blot. HIF-1alpha DNA-binding activity was determined with an ELISA-based kit. HBO-PC increased the proliferation index of endothelial cells and microvascular density at 48 h after partial hepatectomy. The protein level and DNA-binding activity of HIF-1alpha and the protein level of VEGF were increased by HBO-PC before and after partial hepatectomy. Partial hepatectomy alone also increased proliferation index and the expressions of HIF-1alpha and VEGF. Our results indicated that the angiogenesis effect of HBO-PC on liver after partial hepatectomy could be achieved by increased HIF-1alpha activity and VEGF expression. However, the angiogenic effect of HBO-PC is moderate and HBO-PC failed to produce additional effect on the enhancement of HIF-1alpha and VEGF induced by partial hepatectomy alone.
Ren
Ping
P
Department of Pharmacology, China Pharmaceutical University, Nanjing, 210009, PR China.
Kang
Zhiming
Z
Gu
Guojun
G
Liu
Yun
Y
Xu
Weigang
W
Tao
Hengyi
H
Zhang
John H
JH
Sun
Xuejun
X
Ji
Hui
H
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006498:Hepatectomy; D022781:Hepatocytes / Q000378:metabolism; D006931:Hyperbaric Oxygenation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007150:Immunohistochemistry / Q000379:methods; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010100:Oxygen / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D010100:Oxygen