2005 Abstracts: The Regenerative Capacity Is Different in Individual Liver Lobes After Partial Hepatectomy in the Mouse
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The Regenerative Capacity Is Different in Individual Liver Lobes After Partial Hepatectomy in the Mouse
Daniel Inderbitzin, University Hospital Bern, Bern, Bern; Peter Studer, University Hosptial Bern, Bern, Bern, Switzerland; Daniel Sidler, Adrian Keogh, Beat Gloor, Daniel Candinas, University Hospital Bern, Bern, Bern, Switzerland
Background: While developing surgical models of liver regeneration and repair a macroscopically unequal and lobe specific liver regenerative response was observed. We therefore determined the lobe specific hepatic regenerative capacity in individual mouse liver lobes.
Methods: In male Balb/c mice (n=26) partial hepatectomies of varying degrees (i.e. a combination of the resection of the left (L, 34% of total liver mass), the median (M, 26%), the right inferior (RI, 15%), and the caudate lobe (C, 8%)), were performed. BrdU (50mg/kg BW) was injected intraperitoneally 2 hours prior to liver harvest at 24 and 48 hours. Individual liver lobes were dissected, weighed and immunohistochemistry performed to detect BrdU positive cells. The BrdU labelling index was calculated from the data obtained by two independent observers. Results: At 24 hours BrdU positive cells were scarce in all 24 individual liver lobes examined after 26% (M), 60% (L, M), 75% (L, M, RI), and 83% (L, M, RI, C) partial hepatectomy. At 48 hours after 26% (M, n=3) partial hepatectomy an average of 5.3±3.3% BrdU positive nuclei were seen. No significant differences in BrdU labelling were detected between the individual remnant liver lobes (L, right superior (RS), RI, C). After 60% (L, M, n=5) resection average BrdU labelling values were 30.7±16.2% and significantly higher in the RS and RI lobe (37.2±11.6%) than in the C lobe (17.8±17.2%, paired t-test: p<0.05). In the 75% (L, M, RI, n=4) partial hepatectomy group an average of 48.4±7.6% labelled nuclei were seen. No significant differences were detectable between the remnant RS and C lobes. In animals after 83% resection (L, M, RI, C, n=3) BrdU labelling was scant and below 0.01%. Duodenal crypt cells served as internal control for BrdU uptake and were positive in all samples. Linear regression analysis showed a significant correlation (p<0.0001, power 0.98, correlation coefficient 0.90) between the amount of liver tissue resected (26%-75%) and the average BrdU labelling indexes. Conclusions: In surgical models of liver regeneration the hepatic regenerative response is highly dependent on the amount of liver tissue resected. Furthermore, depending on the model used, BrdU incorporation is significantly different in individual remnant liver lobes. The lobe-specific differences observed could prove to be valuable to further dissect the mechanisms of hepatic regeneration and repair in the microsurgical mouse model on a molecular level.
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