线粒体移植改善缺血再灌注损伤的作用及机制

Roles of Mitochondrial Transplantation in Improving Ischemia-reperfusion Injury

当心脏手术、器官移植和血管病变时,血流停止以及之后血液再灌注过程都会对组织器官造成损伤,出现相应的功能障碍,即缺血再灌注损伤(ischemia-reperfusion injury,I/RI)。其中,线粒体功能障碍被认为是器官I/RI的重要原因之一,受损线粒体会导致细胞能量供应减少、活性氧(reactive oxygen species,ROS)生成增加、钙超载等结果,从而激活细胞死亡程序。线粒体是一种高度动态的细胞器,通过不断融合、分裂维持自身稳态,并且,线粒体已被研究证明可在细胞间转移。目前,线粒体提取技术较为成熟,可以从组织中提取出完整的、有活性的线粒体。在以上背景下,出现了线粒体移植(mitochondrial transplantation,MT)技术,通过移植活性线粒体至受损组织内,帮助细胞恢复功能。然而,MT的临床应用还面临着许多挑战,如MT的规范移植程序、作用机制和安全性等仍需要深入研究。本文就近10年MT改善I/RI的作用及相关机制进行了综述。

Ischemia-reperfusion injury(I/RI)is the damage of tissues and organs resulting in different dysfunctions when ischemia and subsequent reperfusion process happen in heart surgery,organ transplantation and vascular diseases.Mitochondrial dysfunction is considered to be one of the important causes of I/RI,because mitochondria damage will lead to energy generation reduction,reactive oxygen species increase and calcium overload,thereby activating the process of cell death.Mitochondria is a highly dynamic organelle,which maintains autogenous homeostasis by fusing and dividing continuously.It has been proven that mitochondria can be transmitted between cells to improve the function of damaged tissues.With the maturity of organelle extraction technology,some scholars have been able to extract functional mitochondria.Therefore,mitochondrial transplantation(MT)appears in above context.The active mitochondria are firstly extracted and purified from healthy tissues,and then transplanted into damaged organs via local or vascular injections.The exogenous mitochondria may fuse with endogenous mitochondria or replace damaged mitochondria DNA after entering the cell by actin internalization.Tissue dissociation and differential filtration is an innovation from McCully’s team,it can separate 2×1010 high-purity functional mitochondria from 0.18 g fresh tissue in less than 30 min.Up to date,the treatment outcomes of MT on heart,brain,kidney,lung and liver acute I/RI have already been more explored.However,there are still many challenges in the clinical application of MT.First of all,there is no standardized transplantation procedure to confirm details,such as dose,mode and time.Secondly,the exact mechanism on MT’s positive action is unclear.Last but not least,further studies on the safety of MT are still needed.This article reviews the role of MT in I/RI treatment and related mechanisms over the past 10 years.