药物预处理在肝脏缺血再灌注损伤中的保护作用研究进展

Research progress on the protective effect of pharmacological preconditioning on hepatic ischemic-reperfusion injury

肝部分切除术和肝移植术是治疗肝脏良恶性肿瘤及终末期肝病的重要方法。肝脏缺血再灌注损伤(HIRI)则是此两类手术中不可避免的难题之一,直接影响手术效果、术后并发症及预后。大量基础及临床研究提示,预处理可以有效减轻HIRI。其中,经典缺血预处理效果确切,但临床实际应用受限;远程缺血预处理临床效果仍存争议;而药物预处理受到更多重视,包括减轻炎症反应或氧化应激反应的药物、抑制特异性酶的药物、改善肝脏微循环的药物、拮抗Ca^(2+)超载的药物等。目前最具临床应用前景的药物包括甲基强的松龙、右美托咪定、乌司他丁、七氟醚、褪黑素等。联合用药可能具有更大潜在价值,但需要更多临床高等级证据支持。本文对临床可减轻HIRI的药物预处理方法进行综述,为接受肝部分切除术或肝移植术患者的早期肝脏功能恢复和远期预后改善提供证据。

Partial hepatectomy and liver transplantation are important methods for the treatment of benign and malignant liver tumors and end-stage liver disease.Hepatic ischemia-reperfusion injury(HIRI)is one of the inevitable problems in these two types of surgery,which directly affects surgical outcomes,postoperative complications and prognosis.A large number of basic and clinical researches demonstrate that preconditioning can effectively mitigate HIRI.Among these approaches,classical ischemic preconditioning has definite effects,but its clinical application is limited.Remote ischemic preconditioning remains controversial in terms of its clinical efficacy.However,more attention has been paid to pharmacological preconditioning,including drugs to alleviate inflammation or oxidative stress response,drugs to inhibit specific enzymes,drugs to improve liver microcirculation,and drugs to antagonize Ca 2+overload.Currently,the most promising drugs for clinical application include methylprednisolone,dexmedetomidine,ulinastatin,sevoflurane,melatonin and so on.Combination therapy may have greater potential value,but more high-level clinical evidence is needed to support it.This paper reviews the clinical methods of pharmacological preconditioning that can alleviate HIRI,providing evidence for early recovery of liver function and improvement of long-term outcomes in patients undergoing partial hepatectomy or liver transplantation.