肝脏缺血再灌注损伤(HIRI)是肝切除手术过程中肝损伤的重要原因,是导致手术不成功的重要原因之一,严重影响患者预后。引起HIRI的机制很多,包括炎症反应、氧化应激、细胞凋亡与自噬、线粒体损伤和钙超载等。近年来越来越多的研究表明,围...肝脏缺血再灌注损伤(HIRI)是肝切除手术过程中肝损伤的重要原因,是导致手术不成功的重要原因之一,严重影响患者预后。引起HIRI的机制很多,包括炎症反应、氧化应激、细胞凋亡与自噬、线粒体损伤和钙超载等。近年来越来越多的研究表明,围术期的麻醉管理可以减轻炎症、抑制细胞凋亡、缓解氧化应激、防止线粒体损伤,从而改善HIRI。本文总结了近年来国内外针对围术期防治HIRI相关麻醉药物的研究进展,旨在总结HIRI主要病理机制和麻醉药物的作用机制,为未来进一步的临床治疗提供依据。Liver ischemia-reperfusion injury (HIRI) is an important cause of liver injury during liver resection surgery and one of the major reasons for unsuccessful surgery, seriously affecting the prognosis of patients. There are many mechanisms that can cause HIRI, including inflammatory response, oxidative stress, cell apoptosis and autophagy, mitochondrial damage, and calcium overload. In recent years, an increasing number of studies have shown that perioperative anesthesia management can reduce inflammation, inhibit cell apoptosis, alleviate oxidative stress, prevent mitochondrial damage, and thus improve HIRI. This article summarizes the research progress of anesthesia drugs for the prevention and treatment of HIRI during the perioperative period at home and abroad in recent years, aiming to summarize the main pathological mechanisms of HIRI and the mechanisms of action of anesthesia drugs, and provide a basis for further clinical treatment in the future.展开更多
目的:研究第10号染色体缺失的磷酸酶张力蛋白同源物基因(phosphatase and tensin homologue deleted on chromosome ten,PTEN)/磷脂酰肌醇3-激酶(phosphoinositide 3-kinase,PI3K)在肝缺血再灌注损伤中的调控作用及可能的机制.方法:夹闭...目的:研究第10号染色体缺失的磷酸酶张力蛋白同源物基因(phosphatase and tensin homologue deleted on chromosome ten,PTEN)/磷脂酰肌醇3-激酶(phosphoinositide 3-kinase,PI3K)在肝缺血再灌注损伤中的调控作用及可能的机制.方法:夹闭C57BL/6J小鼠的肝动脉和门静脉以阻断肝脏向头侧肝叶血供90 min,随后取下血管夹恢复血供,建立肝缺血再灌注损伤模型.实验分为四组:正常对照组(sham)、缺血再灌注模型组(IR)、PTEN抑制剂bpv(HOpic)干预组(BPV+IR)、PI3K抑制剂wortmannin干预组(WM+IR).检测小鼠血清ALT水平,行肝组织病理检查,以评估抑制PTEN/PI3K对肝脏IRI的影响.采用Western blot法检测p-AKT、p-GSK3β的表达,分析抑制PTEN/PI3K对其下游关键效应分子AKT/GSK3β磷酸化的调控.采用定量PCR法检测炎性因子IL-12p40、IL-10及TNF-α的基因表达,分析抑制PTEN/PI3K对TLR4介导的炎症反应的影响.结果:血清ALT及肝组织学改变均提示,抑制PTEN使IR诱导的肝损害明显减轻,相反,抑制PI3K则使IRI加剧.随着再灌注的发生,缺血期去磷酸化的AKT/GSK3β逐渐恢复其磷酸化活性.抑制PTEN增强了再灌注触发的AKT/GSK3β磷酸化,而阻断PI3K则使其明显削弱.阻断PTEN抑制了促炎基因IL-12p40、TNF-α的表达,并使IL-12/IL-10比值下调,该结果与抑制PI3K产生的效应完全相反.结论:PTEN/PI3K在肝缺血再灌注损伤中发挥重要的调控作用,PTEN抑制和/或PI3K活化可能通过上调p-AKT/p-GSK3β以及抑制炎症反应明显减轻肝缺血再灌注损伤.展开更多
文摘肝脏缺血再灌注损伤(HIRI)是肝切除手术过程中肝损伤的重要原因,是导致手术不成功的重要原因之一,严重影响患者预后。引起HIRI的机制很多,包括炎症反应、氧化应激、细胞凋亡与自噬、线粒体损伤和钙超载等。近年来越来越多的研究表明,围术期的麻醉管理可以减轻炎症、抑制细胞凋亡、缓解氧化应激、防止线粒体损伤,从而改善HIRI。本文总结了近年来国内外针对围术期防治HIRI相关麻醉药物的研究进展,旨在总结HIRI主要病理机制和麻醉药物的作用机制,为未来进一步的临床治疗提供依据。Liver ischemia-reperfusion injury (HIRI) is an important cause of liver injury during liver resection surgery and one of the major reasons for unsuccessful surgery, seriously affecting the prognosis of patients. There are many mechanisms that can cause HIRI, including inflammatory response, oxidative stress, cell apoptosis and autophagy, mitochondrial damage, and calcium overload. In recent years, an increasing number of studies have shown that perioperative anesthesia management can reduce inflammation, inhibit cell apoptosis, alleviate oxidative stress, prevent mitochondrial damage, and thus improve HIRI. This article summarizes the research progress of anesthesia drugs for the prevention and treatment of HIRI during the perioperative period at home and abroad in recent years, aiming to summarize the main pathological mechanisms of HIRI and the mechanisms of action of anesthesia drugs, and provide a basis for further clinical treatment in the future.
