Immediate increase of portal pressure, reflecting sinusoidal shear stress, induced liver regeneration after partial hepatectomy

Abstract:

The mechanisms whereby hepatocytes in the normal liver can be primed for replication following partial hepatectomy (PHx) are poorly understood. To determine whether "shear stress," which is induced by acute portal hypertension after PHx, is involved in liver regeneration, we studied liver regeneration in rats with splenic transposition (SPT) in which we can minimize the postoperative elevation of portal pressure. Rats underwent 70% PHx following splenic transposition or sham surgery and were killed at various time points to measure portal pressure and other factors. In the control groups, the portal pressure was significantly increased immediately after surgery, peaking at 48 h, and returning to near the preoperative levels by 168 h after PHx. In the SPT group, although portal pressure increased immediately, it decreased to the control levels 6 h after PHx and thereafter repeatedly increased. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels peaked at 24 and 6 h after PHx, respectively. Proliferative cell analysis was done using MIB-5 antibody, and there were no significant differences between the two groups. Furthermore, liver weight was restored in the same way in both groups. Taken together, the results suggest that an immediate increase in portal pressure is necessary for the initiation of liver regeneration.