Increased NPC1L1 and serum cholesterol in a chronic rejection rat

Purpose: To measure serum cholesterol and triglyceride levels and NPC1L1 mRNA and protein as an index of cholesterol absorption during the development of chronic rejection (CR) in a rat model of intestinal transplantation. Methods: Rats were randomly divided into two groups: Group 1 (n=20) underwent syngenic Lewis-to-Lewis transplantation and Group 2 (n=20) underwent allogenic F344-to-Lewis transplantation as well as treatment with FK506. Blood samples and intestinal tissue were procured on the 190th day after operation. Histological changes were analyzed and the semiquantitative scores of histological parameters were compared. The serum levels of cholesterol and triglyceride were determined. The expression of Niemann-Pick C1 Like 1(NPC1L1) mRNA and protein were analyzed by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) and immunohistochemistry, respectively. Results: All the animals survived for the 190 days. The appearance and histology of isografts were almost normal whereas the allografts displayed thickened bowel wall and mesenteric fibrosis, concentric intimal thickening and interstitial fibrosis and inflammatory in filtration. The histology scores displayed a significant difference between the allografts and isografts (P<0.001). No differences were observed for triglycerides for the two groups. The serum cholesterol levels increased significantly in the allogenic group in comparison with the syngenic group (P=0.034), while no difference was observed for triglyceride levels between groups. RT-PCR showed that the expression of NPC1L1 of allografts increased significantly (P=0.004). Immunohistochemistry confirmed RT-PCR findings. Conclusions: Neointima formation and mesenteric fibrosis were the dominant pathological features. The increased expression of NPC1L1 might contribute to hypercholesterolemia, which may be involved in the pathogenesis of transplant arteriosclerosis.