Effects of cold preservation and warm reperfusion on rat fatty liver

INTRODUCTIONAlthough liver transplantation for irreversible liverdiseases is increasingly prevalent worldwide,patientdie while waiting for donors because of organshortages.One important problem commonlyencountered is that fatty livers often affect theoutcome of liver transplantation.It is reported thatthe incidence of abnormal fatty livers in autopsiesafter accidental death ranged from 15% to 24%.Since fatty livers may result in a primarynonfunction (PNF)liver graft,which contributes

Performance of cold-preserved rat liver Microorgans as the biological component of a simplified prototype model of bioartificial liver

AIM To develop a simplified bioartificial liver(BAL) device prototype, suitable to use freshly and preserved liver Microorgans(LMOs) as biological component. METHODS The system consists of 140 capillary fibers through which goat blood is pumped. The evolution of hema-tocrit, plasma and extra-fiber fluid osmolality was evaluated without any biological component, to characterize the prototype. LMOs were cut and cold stored 48 h in BG35 and Via Span~? solutions. Fresh LMOs were used as controls. After preservation, LMOs were loaded into the BAL and an ammonia overload was added. To assess LMOs viability and functionality, samples were taken to determine lactate dehydrogenase(LDH) release and ammonia detoxification capacity. RESULTS The concentrations of ammonia and glucose, and the fluids osmolalities were matched after the first hour of perfusion, showing a proper exchange between blood and the biological compartment in the minibioreactor. After 120 min of perfusion, LMOs cold preserved in BG35 and Via Span~? were able to detoxify 52.9% ± 6.5% and 53.6% ± 6.0%, respectively, of the initial ammonia overload. No significant differences were found with Controls(49.3% ± 8.8%, P < 0.05). LDH release was 6.0% ± 2.3% for control LMOs, and 6.2% ± 1.7% and 14.3% ± 1.1% for BG35 and Via Span~? cold preserved LMOs, respectively(n = 6, P < 0.05). CONCLUSION This prototype relied on a simple design and excellent performance. It’s a practical tool to evaluate the detoxification ability of LMOs subjected to different preservation protocols.

Warm HTK donor pretreatment reduces liver injury during static cold storage in experimental rat liver transplantation

BACKGROUND： Organ shortage has led to an increased number of transplantations from extended criteria donors. These organs are more vulnerable to ischemia-reperfusion injury. Thus, improvement of organ preservation is needed. HTK is a widely used preservation solution for static cold storage in liver transplantation. The present study was to investigate the beneficial effect of warm HTK donor pretreatment on liver preservation.

A study on liver mitochondria respiration and protein synthesis in cold adapted rats

Mitochondria were isolated from normal and cold adapted rat livers.The respiratory func-tion of mitochondria in rat livers,including ADP:O ratio(P/O)and the respiratory control ratio(RCR),was determined by oxygen electrode method,The protein synthesis in mitochondria wasstudied by observing the incorporation of[~3H]-Leucine into mitochondria.Polyacrylamide gelelectrophoresis was carried out to detect the changes of the inner membrane proteins.It was shownthat the P/O and RCR decreased in cold adapted rats in the 2nd and 4th weeks and returned tothe control level in the 6th week,the protein synthesis of mitochondria decreased significantly incold adapted rats in 1,2 and 4 weeks;the electrophoretic pattern of the inner membrane proteinsin mitochondria from cold adapted rat livers revealed some new bands.

Liver graft preservation methods during cold ischemia phase and normothermic machine perfusion

The growing demand for donor organs requires measures to expand donor pool.Those include extended criteria donors, such as elderly people, steatotic livers,donation after cardiac death, etc. Static cold storage to reduce metabolic requirements developed by Collins in late 1960 s is the mainstay and the golden standard for donated organ protection. Hypothermic machine perfusion provides dynamic organ preservation at 4°C with protracted infusion of metabolic substrates to the graft during the ex vivo period. It has been used instead of static cold storage or after it as short perfusion in transplant center. Normothermic machine perfusion(NMP) delivers oxygen, and nutrition at physiological temperature mimicking regular environment in order to support cellular function. This would minimize effects of ischemia/reperfusion injury.Potentially, NMP may help to estimate graft functionality before implantation into a recipient. Clinical studies demonstrated at least its non-inferiority or better outcomes vs static cold storage. Regular grafts donated after brain death could be safely preserved with convenient static cold storage. Except for prolonged ischemia time where hypothermic machine perfusion started in transplant center could be estimated to provide possible positive reconditioning effect. Use of hypothermic machine perfusion in regular donation instead of static cold storage or in extended criteria donors requires further investigation. Multicenter randomized clinical trial supposed to be completed in December 2021. Extended criteria donors need additional measures for graft storage and assessment until its implantation. NMP is actively evaluating promising method for this purpose.Future studies are necessary for precise estimation and confirmation to issue clinical practice recommendations.

供肝保存液的演变和革新

器官保存液能够改善移植物冷缺血损伤和维持移植物良好的功能。目前,如何减少供肝在冷缺血期间引起的一系列损伤,改善和提高移植物的保存质量,是目前该领域研究的热点和难点。现阶段,临床上的保存液仍未达到理想的保存效果,尤其是对于边缘供器官的保护作用不尽如人意。在当今供者极度匮乏的情况下,为了改善移植物免受冷缺血损伤,其关键要素仍然是寻求最佳的供肝保存方案。本文总结了供肝在冷缺血期间的损伤机制,保存液的分类及供肝保存液的演变历程,探讨了供肝保存液的发展方向及面临的困境,为供肝保存液的研发提供新思路和参考。

低温环境下酪氨酸和半胱氨酸联合刺芒柄花素调控小鼠肝脏产热的机制

探究低温环境下不同浓度刺芒柄花素联合酪氨酸和半胱氨酸的添加对小鼠肝脏产热能力的影响。低温刺激前使用不同添加成分对预饲一周后的小鼠进行为期28 d的灌胃处理。常温对照组每天始终保持在26±2℃环境中饲养,冷暴露组每天置于4℃人工气候室中冷刺激3 h,四周后采集小鼠的肝脏组织。通过HE染色法评估肝脏组织形态;通过免疫组织化学技术定量分析肝组织中UCP1蛋白的表达量;通过Western Blot方法检测肝脏组织中产热因子PGC-1α、PPAR-γ和UCP1的表达水平。结果发现,酪氨酸和半胱氨酸联合刺芒柄花素显著缓解了由冷诱导的小鼠肝细胞内炎性细胞浸润和细胞坏死,并且三者联合显著上调肝脏中产热因子PGC-1α、PPAR-γ和UCP1的表达水平,进而提高小鼠肝脏产热能力。

基于《伤寒论》“热入血室”探讨针刺期门治疗慢性前列腺炎

慢性前列腺炎是临床常见病和多发病,病位在精室,发病和衍变不离热邪,且兼夹湿、瘀、肝郁气滞等。《伤寒论》中共4处论及“热入血室”,条文中描述的血室范畴非女子特有之子宫,亦包括肝脏、冲脉及男子精室,因此“热入血室”可转化为“热入精室”,进而解释慢性前列腺炎的发生并指导治疗。期门属肝经,与精室相连,通过针刺期门疏肝泄热能够对慢性前列腺炎起到针对性治疗效果。针刺期门当重视辨病辨证、合理选经配穴、重视针刺手法,综合运用刺络、扣刺、拔罐等治疗手段,并联合中药诊治方案提高临床疗效。

基于昼夜节律探讨和法治疗恶性肿瘤

“和法”是中医八法之一,应用范围广泛。恶性肿瘤具有一定节律性,应用昼夜节律抗肿瘤取得了良好的效果,但目前尚缺乏针对昼夜节律紊乱有效的干预措施。通过和寒热、和肝脾、和营卫3个方面对“和法”在调节昼夜节律紊乱层面进行探究,并明确和法在恶性肿瘤治疗中的应用,可为肿瘤时间疗法的研究提供参考。

冷缺血时间对不同疾病类型肝组织质量的影响

目的 高质量的肝脏组织样本对肝脏疾病的研究至关重要,冷缺血时间(CIT)是影响组织样本质量的关键因素,探讨冷缺血时间与不同疾病类型肝组织样本质量的相关性,为获得高质量肝组织样本提供标准。方法 选取天津市第一中心医院进行手术治疗的肝癌(HCC)和胆道闭锁(BA)患者各30例,手术切除肝组织后,室温放置0、0.25、0.5、1、2、3、5和6 h后,分别从基因水平、蛋白水平及形态学水平对组织质量进行检测,提取总RNA及基因组DNA,分别检测浓度、纯度及完整性(RIN/DIN值),荧光定量PCR检测组织样本冷缺血0、6 h后ALB基因表达水平;免疫组化方法检测组织样本冷缺血0、6 h后Hep Par1、CK19、CD34、Vimentin蛋白表达情况,Westernblot检测组织样本冷缺血0、6h后ALB蛋白表达水平;HE染色观察组织样本冷缺血0、6 h后组织及细胞形态学变化。结果 DNA产量、RNA纯度和RNARIN随时间变化,时间效应具有统计学意义。组间效应不显著,表明肝癌和胆道闭锁组间没有差异。DNA产量和RNA RIN的交互效应有统计学意义,说明时间的影响随着组别不同而有所不同。与冷缺血0 h相比,肝癌、胆道闭锁组织样本冷缺血6 h后ALB基因表达水平降低,差异具有统计学意义(P <0.05);免疫组化方法检测组织样本冷缺血0、6h后Hep Par1、CK19、CD34、Vimentin蛋白表达情况均无变化,Western blot检测显示组织样本冷缺血0、6 h后ALB蛋白表达水平无显著变化;石蜡切片HE染色显示样本冷缺血0、6 h后组织及细胞形态学无变化。结论 冷缺血时间对肝组织样本中核酸质量具有显著影响,缩短冷缺血时间可获得高质量肝组织样本。

Influence of perfusate on liver viability during hypothermic machine perfusion

AIM: To optimize the perfusates used for hypothermicmachine perfusion(HMP).METHODS: Sprague-Dawley rats were assigned randomly to three groups(n = 12 per group) that received either saline, University of Wisconsin coldstorage solution(UW) or histidine-tryptophan-ketoglutarate solution(HTK) as the perfusate. Each group was divided into two subgroups: static cold storage(SCS) and HMP(n = 6 per subgroup). The liver graft was retrieved according to the method described by Kamada. For the SCS group, the graft was directly placed into cold perfusate(0-4?℃) for 6 h after liver isolation while the portal vein of the graft was connected to the perfusion machine for the HMP group. Then the perfusates were collected at different time points for analysis of aspartate aminotransferase(AST), alanine transaminase(ALT) and lactate dehydrogenase(LDH) levels. Liver tissues were obtained for evaluation of histology, dry/wet weight(D/W) ratio, and malondialdehyde(MDA) and adenosine-triphosphate(ATP) levels. The portal vein pressure and velocity were monitored in real time in all HMP subgroups.RESULTS: Comparison of HMP and SCS: Regardless of the perfusate, HMP improved the architecture of donor graft in reducing the congestion around sinusoids and central vein and maintaining sinusoid lining in morphology; HMP improved liver function in terms of ALT, AST and LDH, especially during the 3-6 h period(SCS vs HMP using saline: ALT3, 225.00 ± 105.62 vs 49.50 ± 18.50, P = 0.047; LDH3, 1362.17 ± 563.30 vs 325.75 ± 147.43, P = 0.041; UW: LDH6, 2880.14 ± 948.46 vs 2135.00 ± 174.27, P = 0.049; HTK, AST6, 307.50 ± 52.95 vs 185.20 ± 20.46, P = 0.041); HMP decreased MDA level(saline, 2.79 ± 0.30 vs 1.09 ± 0.09, P = 0.008; UW, 3.01 ± 0.77 vs 1.23 ± 0.68, P = 0.005; HTK, 3.30 ± 0.52 vs 1.56 ± 0.22, P = 0.006). Comparison among HMP subgroups: HTK showed less portal vein resistance than UW and saline(vs saline, 3.41 ± 0.49 vs 5.00 ± 0.38, P < 0.001; vs UW, 3.41 ± 0.49 vs 4.52 ± 0.63, P = 0.007); UW reduced edema most efficiently(vs saline, 0.68 ± 0.02 vs 0.79 ± 0.05, P = 0.013), while HTK maintained ATP levels best(vs saline, 622.60 ± 29.11 vs 327.43 ± 44.66, P < 0.001; vs UW, 622.60 ± 29.11 vs 301.80 ± 37.68, P < 0.001).CONCLUSION: HMP is superior to SCS in maintaining both architecture and function of liver grafts. Further, HTK was found to be the optimal perfusate for HMP.

Emerging concepts in liver graft preservation

The urgent need to expand the donor pool in order to attend to the growing demand for liver transplantation has obliged physicians to consider the use of suboptimal liver grafts and also to redefine the preservation strategies. This review examines the different methods of liver graft preservation, focusing on the latest advances in both static cold storage and machine perfusion(MP). The new strategies for static cold storage are mainly designed to increase the fatty liver graft preservation via the supplementation of commercial organ preservation solutions with additives. In this paper we stress the importance of carrying out effective graft washout after static cold preservation, and present a detailed discussion of the future perspectives for dynamic graft preservation using MP at different temperatures(hypothermia at 4 ℃, normothermia a t 3 7 ℃ and subnormothermia at 20 ℃- 2 5 ℃). Finally, we highlight some emerging applications of regenerative medicine in liver graft preservation. In conclusion, this review discusses the "state of the art" and future perspectives in static and dynamic liver graft preservation in order to improve graft viability.

Science Letters:A novel way of liver preservation improves rat liver viability upon reperfusion

Background/aim:Currently, the liver is cold-preserved at 0～4 °C for experimental and clinical purposes. Here, we investigated whether milder hypothermia during the initial phase of the preservation period was beneficial for liver viability upon reperfusion. Methods:In the first set of experiments, rat livers were preserved either conventionally in clinically used histidine-trypthopan-ketoglutarate (HTK) solution (Group A:45 min and Group B:24 h) or by slow cooling HTK solution (from 13 °C to 3 °C) during the initial 45 min of preservation (Group C:24 h). In the second set of experiments, additional groups of livers were evaluated:Group BB—preservation according to Group B and Group CC—preservation according to Group C. Further, some livers were preserved at 13 °C for 24 h. Livers were then reperfused using a blood-free perfusion model. Results:Bile production was approximately 2-fold greater in Group C compared to Group B. Alanine transaminase (ALT) and aspartate transaminase (AST) release into perfusate were 2～3-fold higher in Group B compared to Group C. No significant differences were found in ALT and AST release between Group C and Group A. Livers in Group CC compared to Group BB exhibited significantly lower portal resistance, greater oxygen consumption and bromosulfophthalein excretion into bile and lower lactate dehydrogenase (LDH) release into perfusate. Histological evaluation of tissue sections in Group BB showed parenchymal dystrophy of hepatocytes, while dystrophy of hepatocytes was absent in Group CC. Livers preserved at 13 °C for 24 h exhibited severe ischemic injury. Conclusion:These results suggest that the conventional way of liver preservation is not suitable at least for rat livers and that slow cooling of HTK solution during the initial phase of cold storage can improve liver viability during reperfusion.

基于转录组研究饥饿对大黄鱼(Larimichthys crocea)生长和代谢的影响

大黄鱼(Larimichthys crocea)作为我国产量最高、养殖规模最大的海水养殖鱼类,长时间不合理的饥饿易导致养殖效率低下,因此,需要合理控制越冬禁食时间。为了探究饥饿对大黄鱼的影响,在水温9.0~14.3℃条件下进行了饥饿0、8、16周的越冬养殖实验,研究了低温与饥饿双重胁迫下的大黄鱼生长、体成分、抗氧化酶活力以及相关基因的表达。结果显示,随着饥饿时间的延长,大黄鱼的肝体比(HSI)、脏体比(VSI)、肌肉和全鱼的粗脂肪和粗蛋白以及肝糖原含量显著降低(P<0.05),肌糖原含量无显著变化(P>0.05)。肝脏抗氧化酶丙二醛(MDA)活性先升高后降低;谷胱甘肽过氧化物酶(GSH-Px)和过氧化氢酶(CAT)活性显著降低(P<0.05),甘油三酯(TG)含量显著上升(P<0.05)。转录组分析结果显示,相比对照组,饥饿后差异基因显著下调,GO分析发现,饥饿后差异基因主要富集在脂质代谢过程、脂肪酸生物合成和补体激活等方面。聚类分析表明,饥饿16周后,脂肪代谢通路中肉碱棕榈酰转移酶1 (CPT1)、线粒体三功能酶β亚基(HADHB)、肉碱棕榈酰转移酶2 (CPT2)基因的相对表达水平升高,而脂肪酸延长酶(HACD)、脂肪酸合成酶(FASN)、5-氨基乙酰丙酸合成酶(ALAS)基因的相对表达水平下降;免疫代谢通路中丝氨酸蛋白酶抑制剂(SERP)、纤维蛋白原-1 (FGG-1)、纤维蛋白原-3 (FGG-3)、纤维蛋白原β (FGB)基因的相对表达水平也降低,qRT-PCR也证实了以上结果。综上所述,越冬期间,长时间的饥饿将抑制大黄鱼的生长和免疫相关基因的表达,促进其肝脏抗氧化能力和脂质代谢相关基因的表达。

Evaluation of IGL-1 preservation solution using an orthotopic liver transplantation model

AIM: To compare, in a pig liver transplantation model, the protective effect of UW with that of IGL-1, a high-sodium preservation solution containing polyethylene glycol (PEG) as an oncotic supply. METHODS: All livers were harvested and grafted orthotopically according to standard techniques. The livers were washed out and preserved for 7 h in IGL-1 (n = 6) or in UW solution (n = 7) at 4℃. In a sham group (n = 4), the livers underwent a 60-min warm ischemia at 37℃. The hepatocellular injury was assessed in organ preservation solution washed out from the graft at the end of ischemic storage (before revascularization), and in serum 2 h after reperfusion and daily for up to 6 d. RESULTS: Livers preserved in IGL-1 solution released markedly less AST than that preserved in the UW solution before and after revascularization (P < 0.05). Besides, the activity of creatine kinase-BB, a marker of sinusoidal lining cells injury, was higher in the UW group than in the IGL-1 group (P < 0.05). Histological results showed less necrotic regions in livers preserved in IGL-1 solution; however, no difference was observed for in? ammation. CONCLUSION: IGL-1 liquid effectively protects parenchymal and non-parenchymal cells against prese-rvation-reperfusion injuries.

Risk factors of severe ischemic biliary complications after liver transplantation

BACKGROUND:Ischemia-related biliary tract complications remain high after orthotopic liver transplantation.Severe ischemic biliary complications often involve the hepatic duct bifurcation and left hepatic duct,resulting finally in obstructive jaundice.Prevention and management of such complications remain a challenge for transplant surgeons.METHODS:All 160 patients were followed up for at least 180 days after transplantation.One-way analysis of variance (ANOVA) and comparative univariate analysis were made using 3 groups (no complications;mild complications;severe complications),to analyze risk factors associated with biliary complications.Multiple logistic regression and linear regression analysis were used to analyze independent risk factors for severe ischemic biliary complications,after excluding other confounding factors.RESULTS:By ANOVA and comparative univariate analysis,the risk factors associated with biliary complications were preoperative bilirubin level (P=0.007) and T-tube stenting of the anastomosis (P=0.016).Multiple logistic regression analysis showed that the use of T-tube and preoperative serum bilirubin were not independent risk factors for severe ischemic biliary complications after orthotopic liver transplantation.Chi-square analysis indicated that in the incidence of severe ischemic biliary lesions,bile duct second warm ischemic time longer than 60 minutes was a significant risk factor.Linear regression demonstrated a negative correlation between cold preservation time and warm ischemia time.CONCLUSIONS:Preoperative serum bilirubin level and the use of T-tube stenting of the anastomosis were independent risk factors for biliary complications after liver transplantation,but not for severe ischemic biliary complications.The second warm ischemia time of bile duct longer than 60minutes and prolonged bile duct second warm ischemia time combined with cold preservation time were significant risk factors for severe ischemic biliary complications after liver transplantation with grafts from non-heart-beating donors.

Venovenous bypass ahead of mobilization of the liver in orthotopic liver transplantation

BACKGROUND: To evaluate feasibility and safety of venovenous bypass prior to mobilization of the liver during orthotopic liver transplantation (OLT). METHODS: Fifty-four patients were classified into two groups. Group A consisted of 23 patients receiving OLT with classical venovenous bypass. Group B consisted of 31 patients who received a modified-procedure: venovenous bypass ahead of the mobilization of the liver during ULT. The blood loss, duration of venovenous bypass, cold ischemia time, anhepatic phase, and transfusion during operation in the two groups were compared. Complications after the operation were also compared between the two groups. RESULTS: The duration of venovenous bypass and cold ischemia time in group A were longer than those in group B [(99.78±21.36 min) vs (96.32±22.25 min) and (484.78±134.01 min) vs (443.15± 85.27 min)]. The anhepatic phase lasted for about 100 min averagely in the two groups. The volumes of blood loss and transfusion during the operation were larger in group A than in group B [(5096±4243 ml) vs (1726±1125 ml) and (3676±2938.74 ml) vs (1217.69±829.72 ml)]. Postoperative complications occurred in 26 patients of group A and in 19 patients of group B. CONCLUSION: This modified-procedure or venovenous bypass ahead of mobilization of the liver in OLT can reduce the blood loss during OLT and the incidence of postoperative complications without prolongation of the anhepatic phase and duration of venovenous bypass.

Hypothermic machine perfusion with metformin-University of Wisconsin solution for ex vivo preservation of standard and marginal liver grafts in a rat model

AIM To compare the effect of University of Wisconsin(UW) solution with or without metformin, an AMP-activated protein kinase(AMPK) activator, for preserving standard and marginal liver grafts of young and aged rats ex vivo by hypothermic machine perfusion(HMP).METHODS Eighteen young(4 mo old) and 18 aged(17 mo old)healthy male SD rats were selected and randomly divided into three groups: control group, UW solution perfusion group(UWP), and UW solution with metformin perfusion group(MUWP). Aspartate aminotransferase(AST), alanine aminotransferase(ALT), lactate dehydrogenase(LDH), interleukin-18(IL-18), and tumor necrosis factor-alpha(TNF-α) in the perfused liquid were tested. The expression levels of AMPK and endothelial nitric oxide synthase(e NOS) in liver sinusoidal endothelial cells were also examined.Additionally, microscopic evaluation of the harvested perfused liver tissue samples was done. RESULTS AST, ALT, LDH, IL-18 and TNF-α levels in the young and aged liver-perfused liquid were, respectively,significantly lower in the MUWP group than in the UWP group(P < 0.05), but no significant differences were found between the young and aged MUWP groups.Metformin increased the expression of AMPK and e NOS protein levels, and promoted the extracellular release of nitric oxide through activation of the AMPK-e NOS mediated pathway. Histological examination revealed that in the MUWP group, the extent of liver cells and tissue damage was significantly reduced compared with the UWP group.CONCLUSION The addition of metformin to the UW preservative solution for ex vivo HMP can reduce rat liver injury during cold ischemia, with significant protective effects on livers, especially of aged rats.

Aetiology and risk factors of ischaemic cholangiopathy after liver transplantation

Liver transplantation(LT)is the best treatment for endstage hepatic failure,with an excellent survival rates over the last decade.Biliary complications after LT pose a major challenge especially with the increasing number of procured organs after circulatory death.Ischaemic cholangiopathy(IC)is a set of disorders characterized by multiple diffuse strictures affecting the graft biliary system in the absence of hepatic artery thrombosis or stenosis.It commonly presents with cholestasis and cholangitis resulting in higher readmission rates,longer length of stay,repeated therapeutic interventions,and eventually re-transplantation with consequent effects on the patient’s quality of life and increased health care costs.The pathogenesis of IC is unclear and exhibits a higher prevalence with prolonged ischaemia time,donation after circulatory death(DCD),rejection,and cytomegalovirus infection.The majority of IC occurs within 12 mo after LT.Prolonged warm ischaemic times predispose to a profound injury with a subsequently higher prevalence of IC.Biliary complications and IC rates are between 16%and 29%in DCD grafts com-pared to between 3%and 17%in donation after brain death(DBD)grafts.The majority of ischaemic biliary lesions occur within 30 d in DCD compared to 90 d in DBD grafts following transplantation.However,there are many other risk factors for IC that should be considered.The benefits of DCD in expanding the donor pool are hindered by the higher incidence of IC with increased rates of re-transplantation.Careful donor selection and procurement might help to optimize the utilization of DCD grafts.

脂肪变性供肝冷缺血损伤的研究进展

肝移植是治疗终末期肝病的重要手段,然而供者短缺限制了肝移植的发展,如何扩大供肝来源成为学术界的难题。近年来非酒精性脂肪性肝病(NAFLD)供者比例增加,合理利用脂肪变性供肝是扩大供者池的可行方案。肝移植前供肝保存过程的冷缺血损伤增加了术后器官功能不全的发生率。因此了解脂肪变性供肝冷缺血损伤机制和干预措施尤为重要。脂肪变性供肝冷缺血损伤在细胞器层面具体表现为线粒体、溶酶体、内质网的损伤,蛋白层面主要表现腺苷酸活化蛋白激酶(AMPK)、乙醛脱氢酶2(ALDH2)、血红素加氧酶(HO)-1的表达增加。本文就脂肪变性供肝冷缺血损伤的研究进展及相关干预措施做一综述。