Establishment of Acute Liver Failure Model in Tibet Miniature Pig and Verified by a Non-bioartificial Liver

Background and aims Acute liver failure (ALF) is a severe liver disease with high morbidity and mortality. Animal model is very important to research ALF. This study aimed to establish a reproducible, D-galactosamine-induced, Tibet miniature pig model of ALF and verified by a non-bioartificial liver (NBAL).Methods Thirteen Tibet miniature pigs were randomly divided into four groups (A, B, C, D) after central venous catheterization, then D-galactosamine (D-gal) at 0.45, 0.40 and 0.35g/kg body weight were injected through the central venous catheter in group A, B, C. While in group D, D-gal at 0.35g/kg body weight was injected and treated by a NBAL at 48 h after D-gal administration. Vital signs, blood index values were recorded at every 12 h after D-gal administration and every 2 h during NBAL treatemnt. Meanwhile, clinical manifestations, survival times and results of H&E staining, Tunel, Ki67, Masson assays and Picrosirius red staining were performed.Results Tibet miniature pigs developed different degrees of debilitation, loss of appetite and jaundice after D-gal administration. Survival times of groups A, B, C and D were 39.7±5.9 h, 53.0±12.5 h, 61.3±8.1 h and 61±7 h, respectively. Blood levels of ALT, AST, TBIL, Cr, BUN, Amm, PT and inflammation factors (such as TNF-α, IL-1β, IL-6) levels significantly increased compared with baseline in different groups (Ps < 0.05). Pathological results showed obvious liver cell necrosis positively correlated to the dose of D-gal. However, the NBAL did not increase the survival times of ALF, neither Amm and liver cell necrosis, it just decreased some biochemistry indexes (such as TBIL, ALT, AST).Conclusions: We successfully established a reproducible, D-galactosamine-induced, Tibet miniature pig model of ALF, the NBAL did not improve the survival times of ALF and we think the dosage of 0.35 g/kg is optimal.