Lack of protection of ischaemic preconditioning in the rat model of major hepatectomy with ischaemia reperfusion injury.
OBJECTIVE
To investigate the effects of ischaemic preconditioning (IP) on residual liver regeneration after major hepatectomy without portal blood bypass in rats, and to verify whether it can protect the residual liver from ischaemia reperfusion (IR) injury.


METHODS
Ninety rats were randomized into three groups: Group PH, rats were subjected to 70% hepatectomy alone; Group IR, rats were subjected to 30 minutes of total hepatic ischaemia, and 70% hepatectomy was performed just before reperfusion; Group IP, rats were pretreated with IP (5/10 minutes). During the preoperative period and at 0.5, 6, 12, 24 and 48 hours after the operation, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured using an autoanalyser. Serum hyaluronic acid (HA) was measured by radioimmunoassay. Regenerated liver weight (RLW) of the rats was measured and the expressions of Ki-67 and cyclin D1 were determined by immunohistochemistry in remnant liver tissue.


RESULTS
There were no significant differences in serum AST and ALT levels in all the groups before the operation. After partial hepatectomy, AST and ALT levels increased rapidly. From 0.5 to 24 hours after operation, serum AST and ALT levels were significantly higher in IP group rats than in PH and IR rats (p < 0.05). There were no significant differences in serum HA levels in all the groups before the operation. After partial hepatectomy, HA levels increased rapidly, reaching peak values at 12 hours. In the early stage (during 12 hours) after the operation, HA level was significantly higher in IP rats than in PH and IR rats (p < 0.05). The RLW of the rats rapidly increased after partial hepatectomy, and significantly decreased in IP rats compared with PH and IR rats (p < 0.05). Cyclin D1 and Ki-67 expression in all groups before the operation were low and were not significantly different. After partial hepatectomy, they rapidly increased. The expression of Ki-67 and cyclin D1 reached a peak at 24 hours after the operation in PH rats, and they were significantly higher compared with IR and IP rats (p < 0.05). In groups IR and IP, the expression of cyclin D1 and Ki-67 reached peak values at 48 hours. A significant decrease (p < 0.05) was observed after 24 and 48 hours of reperfusion in group IP compared with groups PH and IR.


CONCLUSIONS
IP impairs residual liver regeneration after major hepatectomy without portal blood bypass in rats, and protection from IR injury disappears. IP-induced hyperperfusion may be the cause of reduced liver regeneration.
Qian
Yeben
Y
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China. qianyeben@hotmail.com
Liu
Zhigang
Z
Geng
Xiaoping
X
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D019938:Cyclin D1 / Q000032:analysis; D005260:Female; D006498:Hepatectomy; D006820:Hyaluronic Acid / Q000097:blood; D019194:Ischemic Preconditioning / Q000009:adverse effects; D019394:Ki-67 Antigen / Q000032:analysis; D008115:Liver Regeneration / Q000502:physiology*; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D013997:Time Factors
D019394:Ki-67 Antigen; D019938:Cyclin D1; D006820:Hyaluronic Acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase