Hyperbaric oxygen downregulates hypoxia-inducible factor-1α and inhibits venous neointimal hyperplasia of arteriovenous fistula：an experimental study

Abstract:

Objective：To investigate the effect of hyperbaric oxygen（HBO） on venous neointimal hyperplasia（VNH） of arteriovenous fistula（AVF）. Methods：A total of 36 healthy New Zealand rabbits were randomly divided into sham-operation+renal failure group （sham-operation group），renal failure+AVF+HBO intervention group（experimental group），and renal failure+AVF group（control group），with 12 rabbits in each group. A model of chronic renal failure was established by adenine induction；the rabbits in the experi－mental group and the control group were used to establish a model of AVF，and those in the experimental group were given HBO therapy. Four rabbits were selected from each group on days 7，14，and 28 of HBO intervention，and the vessels of the vein with AVF were collected. HE staining was performed to evaluate intimal thickness，and immunohistochemistry and Western blot were used to measure the expression of hypoxia-inducible factor-1α（HIF-1α），vascular endothelial growth factor（VEGF），and matrix metallopro－teinase-2（MMP-2）. Results：On day 28，VNH was not observed in the sham-operation group，and the mean thickness of VNH was 0.200 5±0.034 0 mm in the experimental group and 0.351 4±0.062 0 mm in the control group；there was a significant difference in the thickness of VNH between the three groups. On day 28，there was a significant difference in HIF-1α MOD between the sham-op－eration group，the control group，and the experimental group（0.003 1±0.000 8 vs. 0.201 6±0.046 1 vs. 0.099 1±0.027 6，P<0.05）. On day 28，VEGF MOD was 0.008 3±0.001 9 in the sham-operation group，0.214 3±0.052 6 in the control group，and 0.105 1±0.040 6 in the experimental group，and there was a significant difference in VEGF MOD between the three groups（P<0.05）. On day 28，MMP-2 MOD was 0.005 1±0.014 6 in the sham-operation group，0.238 4±0.090 3 in the control group，and 0.109 0±0.041 5 in the experimental group，and there was a sig－nificant difference in MMP-2 MOD between the three groups（P<0.05）. On day 28，the expression level of HIF-1α was 0.114 9±0.010 2 in the sham-operation group，0.193 7±0.016 6 in the control group，and 0.151 0±0.018 5 in the experimental group，and there was a significant difference in the expression level of HIF-1α between the three groups（P<0.05）. On day 28，the expression level of VEGF was 0.093 7±0.011 6 in the sham-operation group，0.214 3±0.052 6 in the control group，and 0.238 6±0.008 3 in the experimental group，and there was a significant difference in the expression level of VEGF between the three groups（P<0.05）. On day 28，the expression level of MMP-2 was 0.121 6±0.010 4 in the sham-operation group，0.229 5±0.026 0 in the control group，and 0.175 5±0.011 8 in the experimental group，and there was a significant difference in MMP-2 MOD between the three groups（P<0.05）. Conclusion：HBO therapy can downregulate the expression of HIF-1α，VEGF，and MMP-2 in AVF tissue and significantly inhibit VNH.