血流阻断的缺血预处理技术在肝癌切除术中的应用

目的 探讨缺血预处理(ischemic preconditioning, IP)在血流阻断的伴有肝硬化的肝癌切除中的保护作用机制及临床应用价值。方法 将本院手术切除的34例原发性肝癌患者随机分为2组,IP组18例,肝门阻断切肝前先给予缺血5 min、灌注5 min的缺血预处理;对照组16例,单纯肝门阻断切肝,2组手术由同一组医师完成。比较2组患者手术前后肝功能的变化和肝灌注1 h时肝组织Fas-mRNA表达、Caspase-3活性变化和细胞凋亡的情况。结果 术后1、3、7 d,IP组的血清天门冬氨酸氨基转移酶、丙氨酸氨基转移酶水平明显低于对照组(t=6.985, P<0.01);术后3、7 d,IP组的总胆红素明显低于对照组(t=3.447, P<0.05);术后1 d,IP组的白蛋白高于对照组(t=3.360, P<0.05)。术后1 h,IP组肝组织Fas-mRNA表达、Caspase-3活性和细胞凋亡均明显低于对照组(t=3.771, P<0.05)。结论 IP对肝癌患者入肝血流阻断肝切除术后的肝功能有良好的保护作用,其保护机制是通过下调Fas-mRNA表达和抑制Caspase-3的活性,从而抑制肝细胞凋亡,该技术简便易行值得临床推广应用。

Application of ischemic preconditioning before hepatic vascular exclusion for resection of hepatocellular carcinoma

Objective To assess the value of clinical application of i sc hemic preconditioning (IP) before hepatic vascular ex-clusion for resection of h epatocellular carcinoma (HCC) accompanied by cirrhosis and explore the possible mechanism under-lying the protective effect of this maneuver. Methods Thirty-fou r consecutive patients with resectable HCC were randomized into IP group to rec eive IP with a 5-min ischemia followed by 5-min perfusion before hepatic vascula r exclusion and the con-trol group with simply hepatic vascular exclusion. The l iver function, hepatic Fas mRNA expression, caspase-3 activity, apop-tosis of th e hepatocytes were compared between the two groups. Results In the IP group, the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels on p ostoperative day 1, 3 and 7 were all significantly higher than those of the con trol group (t=6.985, P<0.01). The total bilirubin levels were also higher in the former group on postoperative day 3 and 7 (t=3.447, P<0.05). The IP group had h igher albumin levels on postoperative day 1 than the control group (t=3.360, P<0 .05). After 1 hour's reperfusion, the hepatic mRNA expression of Fas, caspase-3 activity and apoptotic sinusoidal endothelial cells were all significantly hig her than those of the control group (t=3.771, P<0.05). Conclusions IP has a prot ective effect on liver function after hepatic resection with hepatic vascular e xclusion in HCC patients, possibly due to the inhibition of hepatocyte apoptosi s by down-regulating hepatic Fas mRNA expression and caspase-3 activity, and is a convenient technique applicable in such operations as hepatic transplants and hepatectomy.