Effects of splenectomy on hepatic gene expression profiles after massive hepatectomy in rats

Abstract

Background and aim: Possible spleno-hepatic relationships affected by hepatectomy still remained unclear. We have previously reported that splenectomy may ameliorate liver injuries and promote appropriate liver regeneration after massive hepatectomy. Therefore, we investigated the effects of splenectomy on the DNA expression profile in the liver after massive hepatectomy in rats.

Methods: Rats were divided into the following two groups: 90% hepatectomy (Hx group) and 90% hepatectomy with splenectomy (Hx + Sp group). Rats were sacrificed 3 and 6 h after surgery, and mRNA from liver tissue was isolated and hybridized to Affymetrix GeneChip Rat Genome 230 2.0 Array (Affymetrix, Santa Clara, CA, USA) and a pathway analysis was done with Ingenuity Pathway Analysis (Ingenuity Systems, Mountain View, CA, USA).

Results: We determined the Hx + Sp/Hx ratio to assess the influence of splenectomy, and cut-off values were set at more than 2.0-fold or less than 1/2 (0.5)-fold. Immediate early response gene including early growth response-1 and FBJ murine osteosarcoma-related pathways were markedly downregulated by splenectomy. In contrast, heme oxygenase-1 gene-related pathway was upregulated by splenectomy.

Conclusions: Splenectomy provided the protective effects for liver failure and promoted liver regeneration, possibly owing to the downregulation of immediate early response genes and upregulation of the heat shock protein, heme oxygenase-1.

Keywords: early growth response 1; heat shock protein; heme oxygenase-1; hepatectomy; liver regeneration; microarray; reperfusion injury; splenectomy.