Korean J Transplant.  2022 Nov;36(Supple 1):S332. 10.4285/ATW2022.F-4763.

Mammalian target of rapamycin inhibitor attenuates warm ischemic biliary injury (rat model)

Affiliations
  • 1Department of Hepatobiliary and Pancreatic Surgery, Seoul National University Hospital, Seoul, Korea

Abstract

Background
The purpose of this study was to establish a model of warm ischemic biliary injury and evaluate the effects of immunosuppressants (IS) on biliary stricture using this model.
Methods
Fifty Sprague Dawley rats were used. The peribiliary vascular plexus and hepatic artery were ligated. The portal vein was then clamped for 30 minutes following which the rats were divided into three groups; tacrolimus (T), rapamycin (R) admin-istration and no medication (C). Each group consisted of 15 rats, subdivided into three subgroups according to the date of sacrifice for liver tissue sampling (1, 3 and 6 weeks). Serum sampling was performed at postoperative 1 day, 1, 2, 3, 4, 5, 6 weeks in all rats, and enzyme biomarkers of hepatobiliary function were evaluated. Tissues were stained with hematoxylin-eosin and Sirius red for evaluation of biliary stricture. The peribiliary fibrosis was estimated using an image analyzer and the ratio (fibrotic area:normal area) was measured in each slides.
Results
The results revealed no significant difference between groups. Liver tissue obtained at postoperative 6 weeks showed different trends in bile duct proliferation and fibrosis according to IS. The average difference in fibrotic ratio between C and T group was 2.4, and between C and R group was 3.1.
Conclusions
The mammalian target of rapamycin inhibitors (mTORIs) exhibit better protective effects on peribiliary fibrosis compared with calcineurin inhibitors, highlighting the therapeutic potential of mTORIs, in a model of warm ischemic biliary, to counter biliary complications after liver transplantation injury.

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