[Roles of heme oxygenase-1 promoting regeneration of peribiliary vascular plexus in bile duct ischemia/reperfusion injury].
OBJECTIVE
To study the effect of heme oxygenase-1 (HO-1) on peribiliary vascular plexus (PVP) in rat bile duct ischemia/reperfusion injury.


METHODS
Total 128 male SD rats were randomly divided into saline group (Saline), empty virus group (Adv), induced group (Adv-HO-1) and suppressed group (HO-1 siRNA), and there were 32 rats in each group. Rats were injected using 0.5 ml of saline, empty adenovirus, HO-1 adenovirus and siRNA adenovirus (2×10(9) TU/rat) via the dorsal penile vein 24 hours before surgery. Liver function was analyzed at 1 hour and 1, 7, 14 days after reperfusion. HO-1, hypoxiainducible factor-1α (HIF-1α), stromal cell derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF) protein content was analyzed by Western blot. The endothelial progenitor cells (EPCs) ratio in the liver and peripheral blood was detected by flow cytometry. Small vascular around the bile duct was observed by α-smooth muscle actin and von Willebrand factor double immunofluorescence staining.


RESULTS
Reduced liver injury and higher expression of HIF-1α, SDF-1α and VEGF in the induced group after surgery (q = 5.68-7.52, P < 0.01). EPCs ratio in the liver and peripheral blood was significantly higher in the induced group than saline group (q = 12.14 and 15.26, P < 0.01), and the suppressed group at 7 days after surgery were less than saline group significantly (q = 4.83 and 5.07, P < 0.01). In comparison to the suppressed group, higher density of small vascular around the bile duct was seen in the liver tissue of induced group.


CONCLUSIONS
HO-1 can induce the expression of HIF-1α, SDF-1α and VEGF, and mobilize the release of EPCs to the peripheral from the bone marrow. EPCs migrate to the liver and promote damaged PVP repair and regeneration.
Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
Hanfei
H
Huang
Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
Meiling
M
Hou
Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
Jianji
J
Xu
Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
Tianlong
T
Pang
Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
Jian
J
Duan
Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
Zhen
Z
Li
Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China. Email: zzong@medmail.com.cn.
Zhong
Z
Zeng
Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
Kunhua
K
Wang
D000818:Animals; D001652:Bile Ducts / Q000098:blood supply*; D054377:Chemokine CXCL12 / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D018919:Neovascularization, Physiologic; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D013234:Stem Cells / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat