Yousheng Li, Yanfei Zhu, Wei Wei, Jieshou Li

Nanjing University, Nanjing, People's Republic of China

Objective: To observe the effects of fish oil on intestinal cholesterol absorption and pathological changes in chronic rejection (CR), and to study the mechanisms by which long-term fish oil ameliorated graft arteriosclerosis and fibrosis.

Methods: Orthotopic small bowel transplantations were performed from F344 or Lewis donors to Lewis recipients. The recipients were divided into four groups: Group 1, isogenic group, phosphate buffered saline (PBS) (n=8); Group 2, allogenic group, PBS (n=8); Group 3, allogenic group, corn oil (CO) (n=8); Group 4, allogenic group, fish oil (FO) (n=9). CO and FO were supplemented by gavages in 0.6% volume of body weight (0.6%V/W). Rats were sacrificed at POD190. The blood was obtained for detection of cholesterol and triglyceride. The expression of NPC1L1 in jejunum and LXR in liver was analyzed by RT-PCR, Western-blot, Immunohistochemistry and immunofluorescence separately. Graft arteriosclerosis, interstitial fibrosis, inflammatory infiltration and blunting of villi were evaluated by histological observation.

Results: Compared with PBS and CO groups, the serum cholesterol level in FO decreased significantly in FO group, while the triglyceride level showed no difference. Morphology and histology showed mild mesenteric fibrosis, mild intimal thickening and inflammatory infiltration in FO group, while severe pathological changes were observed in PBS and CO groups. Compared with PBS and CO groups, FO group showed the maximal expression of LXR, and the expression of NPC1L1 was lower than PBS group. Immunohistochemistry and immunofluorescence confirmed RT-PCR and Western-blot findings.

Conclusions: Long term intragastrical supplementation with 0.6% fish oil induced the activation of LXR, which induced pronounced inhibition the expression of NPC1L1 expression subsequently. Therefore, it decreased the serum cholesterol level significantly. These might ameliorate the development of graft arteriosclerosis, which provide a possible therapeutic target.