Novel Rat Model of Repetitive Portal Venous Embolization Mimicking Human Non-Cirrhotic Idiopathic Portal Hypertension

作者：Klein Sabine; Hinueber Christian; Hittatiya Kanishka; Schierwagen Robert; Uschner Frank Erhard; Stras**urg Christian P; Fischer Hans Peter; Spengler Ulrich; Trebicka Jonel^*

来源：PLos One, 2016, 11(9): e0162144.

DOI：10.1371/journal.pone.0162144

Background
Non-cirrhotic idiopathic portal hypertension (NCIPH) is characterized by splenomegaly, anemia and portal hypertension, while liver function is preserved. However, no animal models have been established yet. This study assessed a rat model of NCIPH and characterized the hemodynamics, and compared it to human NCIPH.
Methods
Portal pressure (PP) was measured invasively and coloured microspheres were injected in the ileocecal vein in rats. This procedure was performed weekly for 3 weeks (weekly embolization). Rats without and with single embolization served as controls. After four weeks (one week after last embolization), hemodynamics were investigated, hepatic fibrosis and accumulation of myofibroblasts were analysed. General characteristics, laboratory analyses and liver histology were collected in patients with NCIPH.
Results
Weekly embolization induced a hyperdynamic circulation, with increased PP. The mesenteric flow and hepatic hydroxyproline content was significantly higher in weekly embolized compared to single embolized rats (mesenteric flow +54.1%, hydroxyproline +41.7%). Mesenteric blood flow and shunt volumes increased, whereas splanchnic vascular resistance was decreased in the weekly embolization group. Fibrotic markers alpha SMA and Desmin were upregulated in weekly embolized rats.
Discussion
This study establishes a model using repetitive embolization via portal veins, comparable with human NCIPH and may serve to test new therapies.

• 出版日期2016-9-2