Qian Yeben, Liu Zhigang, Geng Xiaoping
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Asian J Surg. 2008 Jul;31(3):140-7. doi: 10.1016/S1015-9584(08)60075-5.
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.
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.
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.
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.
探讨缺血预处理（IP）对大鼠无门静脉转流的大肝切除术后残肝再生的影响，并验证其是否能保护残肝免受缺血再灌注（IR）损伤。
90只大鼠随机分为三组：PH组，仅行70%肝切除术；IR组，行30分钟全肝缺血，再灌注前即刻行70%肝切除术；IP组，予IP预处理（5/10分钟）。术前及术后0.5、6、12、24和48小时，用自动分析仪测定血清天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）活性。采用放射免疫法测定血清透明质酸（HA）。测量大鼠再生肝重量（RLW），并通过免疫组织化学法检测残余肝组织中Ki-67和细胞周期蛋白D1的表达。
术前所有组血清AST和ALT水平无显著差异。部分肝切除术后，AST和ALT水平迅速升高。术后0.5至24小时，IP组大鼠血清AST和ALT水平显著高于PH组和IR组大鼠（p<0.05）。术前所有组血清HA水平无显著差异。部分肝切除术后，HA水平迅速升高，在12小时达到峰值。术后早期（12小时内），IP组大鼠HA水平显著高于PH组和IR组大鼠（p<0.05）。部分肝切除术后大鼠RLW迅速增加，与PH组和IR组大鼠相比，IP组大鼠RLW显著降低（p<0.05）。术前所有组中细胞周期蛋白D1和Ki-67表达均较低，且无显著差异。部分肝切除术后，它们迅速升高。PH组大鼠术后24小时Ki-67和细胞周期蛋白D1表达达到峰值，与IR组和IP组大鼠相比显著更高（p<0.05）。在IR组和IP组中，细胞周期蛋白D1和Ki-67表达在48小时达到峰值。与PH组和IR组相比，IP组再灌注24和48小时后观察到显著降低（p<0.05）。
IP损害大鼠无门静脉转流的大肝切除术后的残肝再生，对IR损伤的保护作用消失。IP诱导的高灌注可能是肝再生减少的原因。
