The Natural history of Liver Regeneration in Rats – Development of an animal model for liver regeneration studies.

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Background: Many suggestions of how and when to assess the regenerated liver in animal models have been proposed. The aim of the present study was to evaluate the natural history of liver regeneration in healthy rats, regarding size, weight and functional capacity. The study was meant as a precursor for further interventional studies in healthy and cirrhotic animals.
Material and Methods: Partial hepatectomy (PHx) of 70% was performed on 64 rats. After PHx the animals were randomised into 8 groups for evaluation. The animals in each group were evaluated on same postoperative day (POD) from POD 1 to 8.
Results: At PHx the animals had a mean body weight of 238.4 g (211.4;286.5). Mean weight of resected liver was 6.25 g (5.2;7.3) and an estimated total liver weight of 8.9 g. Liver weight analysis showed an ascending curve, with max slope POD 1-3, reaching a steady state of ca 9 g on day 5-8. When correlated to body weight, through regeneration rate, a similar pattern was seen, with a RR of 100% reached day 5-8.
Interleukin-6 (Il-6) peaked POD 1 and was falling to undetectable levels day 4. Alfa-2-Macroglobulin (α-2-M) levels were high POD 1-3 before falling to low levels. Tumor-necrosis-factor-alpha (Tnf-α) was undetectable throughout the period.
At the moment functional capacity of the regenerating liver, is analysed by the enzymatic method BTR (Ratio of Branched-Chain Amino Acids to Tyrosine)
Stereological aspects are looked into regarding KI-67 analysis and blood vessel density estimation, as is more serological markers (Alanin-amino-transferase, Bilirubin, Alkaline-phosfatase and Hepatocyte-growth-factor).
Conclusion: Liver regeneration, regarding size and weight, were at top speed day 1-3. Full liver regeneration reached a plateau after 5-8 days, and should after this point be considered practically at end.
Liver regeneration should in further studies be evaluated on postoperative day 1, 3 and 8.
StatusUdgivet - 2013

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