Published online Jan 21, 2018. doi: 10.3748/wjg.v24.i3.360
Peer-review started: October 17, 2017
First decision: October 31, 2017
Revised: November 7, 2017
Accepted: November 27, 2017
Article in press: November 27, 2017
Published online: January 21, 2018
Processing time: 94 Days and 6.9 Hours
To investigate the effect of ischaemia and reperfusion (I/R) injury on the Ca2+-ATPase activation in the intestinal tissue of a rat autologous orthotopic liver transplantation model and to determine if hypoxia preconditioning (HP) therapy induces HIF-1α to protect rat intestinal tissue against I/R injury.
Rats received non-lethal hypoxic preconditioning therapy to induce HIF-1α expression. We used an autologous orthotopic liver transplantation model to imitate the I/R injury in intestinal tissue. Then, we detected the microstructure changes in small intestinal tissues, Ca2+-ATPase activity, apoptosis, and inflammation within 48 h postoperatively.
HIF-1α expression was significantly increased in intestinal tissue at 12 h postoperatively in rats that were exposed to a hypoxic environment for 90 min compared with a non-HP group (HP vs AT, P = 0.0177). Pathological analysis was performed on the intestinal mucosa cells, and the cells in the HP group appeared healthier than the cells in the AT group. The Ca2+-ATPase activity in the small intestinal cells in the AT group was significantly lower after the operation, and the Ca2+-ATPase activity in the HP group recovered faster than that in the AT group at 6 h postoperatively (HP vs AT, P = 0.0106). BCL-2 expression in the HP group was significantly higher than that in the AT group at 12 h postoperatively (HP vs AT P = 0.0010). The expression of the inflammatory factors NO, SOD, IL-6, and TNF-α was significantly lower in the HP group than in the AT group.
Hypoxia-induced HIF-1α could protect intestinal mucosal cells against mitochondrial damage after I/R injury. HP could improve hypoxia tolerance in small intestinal mucosal cells and increase Ca2+-ATPase activity to reduce the apoptosis of and pathological damage to intestinal cells. HP could be a useful way to promote the earlier recovery of intestinal function after graft procedure.
Core tip: Ischaemia/reperfusion (I/R) injury affects the recovery of postoperative bowel function in liver transplantation. In our research, hypoxia-induced HIF-1α expression could protect mitochondrial function and Ca2+-ATPase activity against I/R injury to reduce the apoptosis and pathological damage to intestinal cells. Therefore, we suggest that hypoxic preconditioning therapy could improve the tolerance of small intestinal mucosal cell to hypoxia in rat autologous orthotopic liver transplantation.