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P-4.69 Double-lobectomy in rat model of steatotic liver transplantation

Fu Zhen, People's Republic of China

Institute of Hepatobiliary Diseases of Wuhan University

Abstract

Double-lobectomy in rat model of steatotic liver transplantation

Fan Lin1, Fu Zhen1, Xiong Yan1, Ye Shao Jun1, Wang Yan Feng1, Peng Gui Zhu1, Ye Qi Fa1,2.

1Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Wuhan, People's Republic of China; 2The 3rd Xiangya Hospital of Central South University, Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, Changsha, People's Republic of China

Aim of present study was to establish a stable rat model of steatotic liver transplantation for marginal liver grafts (MLG) researches and reduce the number of animals being used in experiment. Male Sprague - Dawley rats were fed with high-fat diet (HFD; 60 %, kJ) or standard chow diet (SCD) for 8 weeks. The Liver enzymes and lipid level were detected by kits every week. The degree of steatosis was evaluated with hematoxylin-eosin and Oil Red O staining. The comparison of post-transplantation survival of SD rats were assessed in two groups. Compared with SCD group, the levels of ALT and AST had no significant change in HFD group (P > 0.05). In HFD group, plasma triglyceride (TG) level ascended approximately doubled during the first 2 weeks (P < 0.01), decreased to baseline levels between 3rd and 8th week (P > 0.05). Levels of plasma glucose, portal insulin and content of liver lipid were increased in HFD group when comparing with SCD group and the difference was statistically significant (P < 0.05, P < 0.05 and P < 0.01, respectively). After 6 weeks, the steatosis of rat liver tended to be stable. Rat liver developed with hepatic macrovesicular steatosis > 60 % was procured for transplantation after two lopes reduced. Post-transplantation survival rate (HFD vs SCD): 1 - week 80% vs 100% , 1 - month 20% vs 100%, respectively. 20 rats were saved from being scraficed by using double-lobectomy for biopsy. Our present study reveals that rat liver double-lobectomy, as a self-control method, could be well applied in steatotic LT or other relevant researches without enlarging the amount of animals being used, promoting animal welfare.

National Natural Science Foundation of China, Grant No. 81970548. Medical Science Advancement Program (Youth Scholars) of Wuhan University, Grant No. TFZZ2018035. Zhongnan Hospital of Wuhan University Science, Technology and Innovation Seed Fund, Project ZNPY2018010.. Fundamental Research Funds for the Central Universities (No. 2042019kf0133).

References:

[1] McCormack L, Dutkowski P, El-Badry AM, Clavien PA.Liver transplantation using fatty livers: always feasible? J Hepatol 2011;54:1055-1062.
[2] Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology .2004;40:1387-1395.
[3] GabrielliM, Moisan F, VidalM, et al. Steatotic livers. Can we use them in: OLTX? Outcome data from a prospective baseline liver biopsy study. Ann Hepatol. 2012;11:891-898.
[4] Spitzer AL, Lao OB, Dick AA, et al. The biopsied donor liver:incorporating macrosteatosis into high-risk donor assessment.Liver Transpl . 2010;16:874-888.

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