Volume 8 Issue 2
Mar.  2017
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Li Xiao, Ji Hongchen, Dou Kefeng, et al. Study on SCARB1 mediated coagulation dysregulation in recipients after liver xenotransplantation[J]. ORGAN TRANSPLANTATION, 2017, 8(2): 115-120. doi: 10.3969/j.issn.1674-7445.2017.02.005
Citation: Li Xiao, Ji Hongchen, Dou Kefeng, et al. Study on SCARB1 mediated coagulation dysregulation in recipients after liver xenotransplantation[J]. ORGAN TRANSPLANTATION, 2017, 8(2): 115-120. doi: 10.3969/j.issn.1674-7445.2017.02.005
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Study on SCARB1 mediated coagulation dysregulation in recipients after liver xenotransplantation

doi: 10.3969/j.issn.1674-7445.2017.02.005

  • Department of Hepatobiliary Surgery, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China

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    Abstract
  •   Objective  To investigate the changes in the expression levels of scavenger receptor class B member 1 (SCARB1) in the liver tissues before and after liver xenotransplantation and analyze the relationship between the variations in the SCARB1 expression and coagulation regulating dysfunction in the recipients.  Methods  The Wuzhishan miniature pig with α-1, 3-galactosyl-transferase gene-knockout (GTKO) was utilized as the donor and Macaca thibetana was chosen as the recipient. Heterotopic auxiliary liver xenotransplantation models were established. The liver tissue specimen was collected before and after liver xenotransplantation. Primary hepatocytes were extracted from the pig using collagenase digestion method. Human peripheral blood mononuclear cells were obtained by immunomagnetic bead sorting. These two types of cells were co-cultured and supplemented with human plasma to establish cell models with coagulation regulating dysfunction following liver xenotransplantation. Quantitative real-time polymerase chain reaction (RT-PCR) and Western blot were performed to quantitatively measure and statistically compared the expression levels of messenger ribonucleic acid (mRNA) and protein of SCARB1 in the tissue and cell samples. At the cellular level, the expression of SCARB1 was interfered by lentiviral vector. The coagulation time was detected to validate the effect upon coagulation function.  Results  The expression levels of SCARB1 mRNA and protein were significantly down-regulated after liver xenotransplantation (both P < 0.05). In the cell models, the expression levels of SCARB1 mRNA and protein in the porcine hepatocytes co-cultured with human monocytes were significantly down-regulated compared with those in porcine hepatocytes without intervention (both P < 0.05). Compared with the non-intervention group, the coagulation time was significantly prolonged after the expression of SCARB1 was interfered by lentiviral vector (P < 0.05).  Conclusions  The down-regulated expression of SCARB1 in the liver graft is one of the main causes of mediating coagulation regulating dysfunction. Intervention of SCARB1 expression contributes to resolve the coagulation regulating dysfunction in the recipients after liver xenotransplantation.

     

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