Role of 5-hydroxy trptamine 2A receptor in biliary fibrosis after liver transplantation in rats
10.3760/cma.j.issn.0254-1785.2014.09.011
- VernacularTitle:5-羟色胺受体2A在大鼠肝移植术后胆管纤维化中的作用
- Author:
Liping CHEN
;
Yawen WANG
;
Li XIAO
;
Wenmei FAN
;
Bingyi SHI
- Publication Type:Journal Article
- Keywords:
Rats;
Liver transplantation;
Biliary fibrosis;
5-hydroxytryptamine
- From:
Chinese Journal of Organ Transplantation
2014;35(9):555-560
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the role of 5-hydroxy trptarine 2A receptor (5-HT2A) in the pathogenesis of biliary fibrosis after liver transplantation in rats.Method Rats were randomly divided into control group Ⅰ and control group Ⅱ[(supplied livers were preserved for 1 or 12 h),ketanserin group (recipients of control group Ⅱ were intraperitoneally injected with ketanserin 24 h postoperatively at the dosage of 5 mg · kg-1 · day-1),and sham group (rats were subjected to transverse laparotomy and closure without manipulation of the liver).During 4-week observation period,serum biliary enzymes,5-HT content in the liver,the expression of fibrosis-related genes,cholangiocytes proliferation and biliary fibrosis were evaluated.Result Compared with the sham group,the serum ALP,GGT,TBil and 5-HT contents in the liver homogenate were increased on the postoperative day 1 (POD1) and then restored to the normal level.There was slight proliferation of bile duct epithelial cells on POD3 in the control group Ⅰ,with fewer collagen fibers and α-sooth muscle actin (α-SMA)-positive myofibroblasts in the portal area.The expression of matrix metalloproteinase-2 (MMP-2) and procollagen α1-mRNA in graft livers was not significantly increased in the control group Ⅰ.To the contrast,the control group Ⅱ demonstrated high levels of serotonin in the liver homogenate and enhanced serum biliary enzymes.Active cholangiocytes proliferation was triggered on POD3 and remained higher than in the control group Ⅰ and the sham group.The control group Ⅱ showed a large number of α-SMA-positive myofibroblasts and collegan fibers at the postoperative week 4.In parallel,the major profibrogenic transcripts MMP2 and procollagen α1 were significantly increased at 2nd,and 4th week postoperation in the control group Ⅱ.Importantly,we also found that ketanserin relieved the signs of biliary fibrosis at 4th week postoperation in 5-HT2A group by the demonstration of reduced collagen fibers and a-SMA-positive myofibroblast in the portal area,as well as the decrease in the fibrosis-related gene expression.In addition to the lower cholangiocytes proliferation,serum levels of biliary enzymes including GGT,ALP and TBil in 5-HT2A group were significantly decreased at 4th week postoperation as compared with the control group Ⅱ.Conclusion Selective 5-HT2A receptor antagonist,Ketanserin retards biliary fibrosis progression posttransplantation,suggesting that 5-HT2A receptor is a potential therapeutic target for ischemia-related biliary fibrosis after DCD liver transplantation.
