肝细胞急性坏死与凋亡的磁共振扩散加权成像活体检测实验研究

 目的 评价MRI、DWI检测及鉴别肝细胞凋亡和坏死两种病理改变的价值.方法 72只S-D大鼠随机分成假手术对照组、右侧肝动脉与门静脉分支均结扎组(HA+PV组)和单独右侧门静脉分支结扎组(PV组),各24只.每组再分成4个亚组,每个亚组6只,分别于术后3 h、12 h、24 h、72 h行MRI、DWI检查,检查结束后取肝标本作HE染色、TUNEL染色,将病理结果与影像检查进行对照分析.结果 右侧门静脉与肝动脉均结扎后,肝右叶于术后3 h在T2WI上即表现为高信号,ADC值下降.单独肝右侧门静脉结扎后12 h,肝右叶ADC值出现升高,至24 h肝细胞凋亡数达最高,ADC值也达最高.结论 T2WI和DWI可早期检测发生坏死的肝组织.而组织中细胞发生凋亡后,DWI较T1WI、T2WI早期检测到凋亡组织.     

肝组织坏死和凋亡MRI鉴别诊断的实验研究

目的:通过对大鼠肝右叶坏死和凋亡的动物模型进行磁共振T1WI、T2WI、DWI和ADC等检查,观察形态和信号变化特点,探索MRI新技术对肝脏组织坏死或凋亡的鉴别诊断能力。材料和方法:78只大白鼠随机分成13组,每组6只,A1、B1、C1、D1、E1、F1六组动物同时结扎肝动脉右支和门静脉右支。A2、B2、C2、D2、E2、F2六组动物单独结扎门静脉右支,另6只大鼠为假手术对照组。各组实验大鼠于手术后3h、12h、24h、3d、7d、14d进行MRI检查,然后处死动物并取得肝脏标本,进行HE染色、TUNEL染色、透视电镜等病理检查。每例均进行常规MRI和DWI、ADC图成像。结果:动物麻醉和结扎手术成功率93.8%。右侧肝动脉与门静脉分支均结扎后,病理显示肝右叶发生凝固性坏死。单独右侧门静脉分支结扎后,3h即出现凋亡细胞,24h达高峰。坏死肝组织在DWI上早期即呈高信号,中晚期呈长T1和中等T2表现。单纯门静脉右支结扎的A2、B2、C2组大鼠肝右叶在T1WI上呈特征性较高信号,T2WI呈等信号,72h后出现斑点状高信号,DWI上早期呈信号减低改变,后期呈等信号或小片状高信号。结论:肝组织细胞坏死和凋亡在T1WI和T2WI上有明显的信号差异表现。结合DWI和ADC检查表现,可以区分肝脏细胞发生坏死或凋亡的不同病理改变。     

肝细胞急性坏死与凋亡的磁共振波谱研究

 目的 建立大鼠肝细胞坏死和凋亡的动物模型,将不同时间点的MRS检测结果与病理学所见进行对照研究,以评估MRS检测及鉴别肝细胞凋亡和坏死的能力与价值.方法 72只S-D大鼠随机分成假手术对照组、右侧肝动脉与门静脉分支均结扎组(HA+PV组)和单独右侧门静脉分支结扎组(PV组),实验组各分成4个亚组,每个亚组6只,分别于术后3 h、12 h、24 h、72 h行普通MRI和单体素PRESS 35序列MRS,得到肝右叶与左叶各代谢物浓度,以及肝右叶内代谢物相对比值.结果 HA+PV及PV组术后3 h,少量肝细胞发生坏死与凋亡时,肝右叶Lip-Lac较左叶相比即有明显增高,随着凋亡与坏死细胞增多,Lip-Lac增高更加明显.术后12 h肝右叶Cho较左叶相比出现降低,也随时间延长逐渐明显;肝右叶Lip-Lac/Cho比值在HA+PV及PV组术后3 h均有增高,以PV 3 h组增高更显著.结论 凋亡与坏死组织在1H MRS中都有Lip-Lac增加,Cho降低.肝细胞凋亡后早期,Lip-Lac/Cho比值增高较坏死明显,采用Lip-Lac/Cho比值对鉴别早期肝细胞坏死与凋亡具有一定意义.     

大鼠右肝血供不同程度阻断后的病理变化及磁共振表现

目的:探讨用磁共振新技术活体检测肝细胞凋亡和坏死的可能性。方法:①体重为0.25～0.3kg的SD大鼠90只随机分成A、B、C三组,每组30只,分别行右肝门静脉结扎(A组)、右肝门静脉及肝动脉双结扎(B组)及假手术(C组),术后3h、1天、3天、7天、14天作为5个时间点,各观察6只。②每组大鼠进行磁共振成像(MRI)、磁共振扩散加权成像(DWI)、1H磁共振波谱(1H-MRS)及磁共振灌注成像(PWI)检查。③取肝脏标本行病理学及电镜检查。④将磁共振检查结果同病理学及电镜对照分析。结果:①A组病理学及电镜检查证实肝细胞发生凋亡;B组肝组织发生凝固性坏死。②A组T1WI信号增高,T2WI信号刚开始略减低,后呈小片状增高;DWI呈小片状高信号,表观扩散系数(ADC)图则相反;MRS表现为胆碱(Choline,Cho)、肌酸(Creatine,Cr)、谷氨酸(Glutamate,Glx)峰稍下降,乳酸(Lactate,Lac)峰、脂质(Lipid,Lip)峰增加;PWI灌注曲线下降;③B组T1WI信号减低,T2WI信号增高;DWI呈高信号;Cho峰下降明显,Cr、Glx峰下降,Lac峰明显升高,Lip峰略增高;PWI曲线低平。结论:右肝血供不同程度阻断后肝细胞分别发生凋亡和坏死;磁共振检查(DWI、MRS、PWI)具有特征性表现,可活体检测细胞凋亡和坏死的存在。     

肝组织大面积凋亡的磁共振成像和病理对照研究

目的:通过手术结扎大鼠门静脉右支的方法制作肝组织大面积凋亡的动物模型,并通过MRI和病理学方法对其进行对照研究,评价MRI、DWI和增强MRI对肝脏大面积凋亡的诊断价值.材料和方法:采用S-D大鼠42只,随机分7组.A组为假手术对照组,B、C、D、E、F、G组大鼠分别于门静脉右支结扎后3h、12h、24h、3d、7d、14d进行磁共振成像,检查结束后进行肝脏标本病理检查,包括HE染色、TUNEL染色.将病理结果与MRI、DWI和增强MRI资料进行对照分析.结果:通过门静脉分支结扎成功制作肝细胞大片凋亡的动物模型.肝细胞大片凋亡早期在T1WI上呈略高信号,T2WI上为中等略低信号,随时间延长至72h,T2WI上肝右叶内可见斑片状稍高信号灶,在T1WI上仍为低信号.在DWI上以等低信号或肝叶内出现斑片状稍高信号影为主.增强MRI早期,病灶部位表现为明显均匀强化,但是在门脉期增强明显低于肝左叶.结论:肝组织发生大片细胞凋亡后在普通MRI、增强MRI成像和DWI上均有较明显的特征性表现,各种序列综合表现可以较早期和较敏感地显示肝组织细胞大片凋亡的存在.     

经胆管192Ir内照射对犬胆管周围肝组织放射损伤的实验研究

目的:通过研究经胆管192Ir内照射(192Ir-internalirradiation,192 Ir-IIR)对胆管周围肝组织放射损伤,探讨经胆管192 Ir-IIR的有效治疗范围。方法:实验动物为雄性健康杂种犬4只,体重25~30kg。经手术将施源管植入胆管,根据预先设定的剂量及照射点进行胆管内近距离照射。放射源采用192Ir。内照射10天后处死动物,距离胆管壁由近及远按设计距离分别取1mm×1mm×1mm大小肝组织,常规制备光镜切片,作TUNEL染色;同时常规制备电镜切片。光镜下观察周围肝组织的放射损伤同时计数凋亡肝细胞。电镜下观察肝组织超微结构损伤变化并计数凋亡肝细胞。结果:在胆管最大耐受剂量50Gy时,距胆管15mm内肝细胞核出现不可逆性改变。结论:距放射源15mm可以作为有效治疗范围。     

去胆管肝叶肝组织形态及功能变化的实验研究

目的观察大鼠肝叶胆管栓塞结扎后肝细胞形态及功能的变化,探讨去胆管肝叶的保留价值。方法应用氰基丙烯酸酯对仅保留肝右叶和方叶的大鼠行右叶胆道栓塞并结扎,制备去胆管肝叶,肝方叶不处理或行门静脉结扎作去门脉肝叶自身对照。通过分肝静脉血化验检查、组织学观察探讨肝细胞形态及功能的变化。结果与假手术对照组及自身未处理肝叶相比,去胆管肝叶萎缩不明显,超微结构变化不大。透射电镜观察发现去胆管肝叶肝细胞富含线粒体、核糖体及粗面内质网。PAS染色显示肝糖原代谢也无明显差别。分肝静脉血白蛋白及纤维蛋白原含量无明显减低。结论去胆管肝叶在观察期内无明显纤维化,仍保留有肝细胞蛋白质合成、分泌及营养物质代谢功能,提示去胆管肝叶具有保留价值。本实验为临床特殊情况下结扎或切除胆管而保留相应的肝脏组织提供了理论基础。     

单侧门静脉栓塞诱导家兔肝细胞凋亡及对侧肝叶增生的实验研究

目的探讨家兔门静脉栓塞后同侧肝细胞凋亡及对侧肝叶增生的最佳时间。方法健康家兔40只,随机分成5组,每组8只。一组做对照,余剖腹细针穿刺行肝右叶选择性门静脉栓塞。分别于栓塞前、栓塞后第3、7、14、21天各处死1组,依次为A、B、C、D、E组。处死后测量肝左、右叶体积,右肝取病理切片观察肝细胞凋亡、坏死情况及肝功能改变。结果栓塞后肝右叶体积逐步减少,A到E组平均体积分别为46．4、46．0、44．4、42．0、39．7 cm~3。肝左叶体积逐步增大,A到E组平均体积分别为54．0、54．5、56．3、61．7、63．9 cm~3。剩余肝比例逐步增加,A到E组分别为53．8%、54．2%、55．9%、59．0%、61．0%。肝细胞凋亡指数A到E组分别为8．1%、12．2%、19．4%、20．1%、14．2%。结论选择性门静脉栓塞可引起同侧肝叶萎缩及诱导肝细胞凋亡和对侧肝叶体积代偿性增生,最佳时间为7～14 d。     

部分门静脉动脉化后肝门部胆管细胞增生的实验研究

目的 了解部分门静脉动脉化后大鼠肝门部胆管上皮细胞的增生改变情况.方法 30只SD大鼠随机分为对照组(A组)、肝总动脉结扎+胆管再通组(B组)及部分门静脉动脉化+胆管再通组(C组),每组10只.A组仅游离肝动脉、门静脉及胆管,不做其他处理,B、C组进行相应的处理.于造模后1个月,取大鼠静脉血检测肝功能的改变,随后处死大鼠取肝门部胆管,行免疫组化染色,检测各组胆管上皮细胞核增生情况和肝门部胆管的病理改变.结果 各组大鼠术后均存活.与A组比较,B、C两组胆管细胞表现出较明显的增生,以B组增生最为明显(P＜0.01).三组间碱性磷酸酶水平比较无显著性差异(P＞0.05);与A、C组(0.520±0.155,0.590±0.251U/L)比较,B组的γ-谷氨酰胺转移酶水平(0.740±0.135U/L)更高.差异有统计学意义(P＜0.05).与A、C组比较,B组肝门部胆管表现出明显的慢性增生性炎症改变.结论 部分门静脉动脉化可以明显减轻肝动脉结扎后所致的肝门部胆管损伤,满足肝门部胆管的动脉血供需求.     

血管硬化剂肝动脉灌注栓塞对兔门静脉损伤的实验研究

目的:观察血管硬化剂(平阳霉素碘化油乳剂PLE和无水乙醇)在行肝动脉栓塞治疗中对门静脉造成的损伤,对其出现的可能相关因素进行分析。方法:60只实验兔随机分成实验1组与实验2组和对照组,每组20只。在X线监视下,经股动脉插管至兔肝动脉,行肝动脉栓塞。实验1组注射平阳霉素 超液态碘化油;实验2组注射无水乙醇 超液态碘化油;对照组灌注超液态碘化油。术后分别于3、5、7天处死,开腹取出Glisson鞘中组织,分别作光镜及电镜观察。统计出发生门静脉损伤的兔例数,进行统计学分析。结果:实验1组光镜下出现门静脉损伤5例,电镜下6例,与对照组相比具有显著性差异(P<0.05);实验2组在光镜和电镜下分别有7例出现门静脉损伤,与对照组相比具有显著性差异(P<0.05)。实验1组与实验2组比较统计学分析没有显著性差异(P>0.05)。结论:经兔肝动脉在一定压力下注射血管硬化剂会造成门静脉的损伤,且不同的血管硬化剂造成的损伤程度不同。     

Assessment of future remnant liver regeneration after portal vein embolization using three-dimensional CT and MR volumetric analyses

The purpose of this study is to portray right portal vein embolization (PVE) as a valuable technique that helps in expanding the volume of the left liver lobe and discuss the relevant published work. We describe our experience with four patients who underwent PVE and analyse the value of CT and MRI in the preoperative evaluation of these patients. Four patients with hepatic malignancy (hepatocellular carcinoma) (n=2) and metastatic liver disease (n=2) underwent portal vein occlusion. PVE was carried out in three patients using polyvinyl alcohol and stainless steel coils. Portal vein ligation was carried out in the fourth patient. In patients who were candidates for right hepatectomy, CT volumetric analysis was carried out before the surgery to assess the total liver volume and the future remnant liver, which is the residual left hepatic volume (in cases of right hepatectomy) or left lateral segment volume (in cases of right tri-segmentectomy). Because the left lobe volumes were insufficient, patients were selected to undergo right PVE. Computed tomography volumetry was carried out 2-4 weeks after embolization to assess left hepatic lobe regeneration. Magnetic resonance volumetric analysis was carried out in two patients before and after embolization. All four patients had significant regeneration of the left lobe and tolerated the surgery with uneventful postoperative recovery.     

Portal vein ligation is as effective as sequential portal vein and hepatic artery ligation in inducing contralateral liver hypertrophy in a rat model

PURPOSE: Dual embolization of the hepatic artery and portal vein (PV) has been proposed to enhance contralateral liver regeneration before resection. The aim of this study was to evaluate the effect of PV ligation compared with simultaneous or sequential dual ligation on regeneration, proinflammatory response, and liver damage. MATERIALS AND METHODS: Single hepatic artery ligation (HAL), PV ligation (70%), or dual ligation of the hepatic artery and PV (70%) simultaneously or sequentially within a 48-hour interval was performed in a rat model. Liver regeneration, proinflammatory mediators, hepatocellular synthetic function and injury, histopathology, and apoptosis were assessed at a maximum of 14 days after surgery. RESULTS: Sequential dual ligation resulted in a faster increase in hepatocyte proliferation at 24 hours without additional increase in liver mass compared with PV ligation after 14 days. Both dual ligations significantly increased proinflammatory response in plasma and in the regenerating liver compared with PV ligation alone. Fourteen days after PV ligation, the hepatic parenchyma was completely restored, whereas fibronecrosis was seen in the sequentially dual-ligated groups and complete necrosis was seen in simultaneously ligated groups. Increased apoptosis in the regenerating liver and prolonged hepatic dysfunction were observed after both dual ligations. CONCLUSIONS: PV ligation is as effective as dual ligation in inducing liver regeneration. No additional benefit of arterial ligation was observed.     

经皮门静脉栓塞治疗肝癌的临床应用

目的探讨经皮选择性门静脉右支栓塞(PVE)在肝癌治疗中的应用价值。方法12例无手术切除指征的中晚期肝癌患者,在电视透视引导下经导管行经皮穿肝或穿脾行PVE。栓塞前、后用CT测量左侧肝叶的体积,并测量栓塞前后的门静脉压力、肝功能。结果12例患者均成功行经皮PVE,栓塞术后左肝叶代偿增生明显,其中3例PVE后顺利实行右肝切除术。PVE后未出现门静脉高压,肝功能损害轻,均未发现并发症。结论经皮选择性PVE能诱导非栓塞侧肝叶代偿性增生及栓塞侧肝叶萎缩,增加肿瘤手术切除机会,提高手术切除的安全性,对于无法手术切除的肝癌患者重新获得手术切除的机会,具有潜在的临床应用价值。     

门静脉阻断兔肝VX2移植瘤的DSA评价

目的评价DSA在兔肝VX2移植瘤经门静脉阻断后显示肝动脉与门静脉的价值。方法20只新西兰大白兔随机分为移植瘤体生长3周后门静脉阻断组和移植瘤体未行门静脉阻断对照组,2周后分别行兔肝动脉与门静脉DSA检查。结果DSA在肝动脉分支的显示效果上较血管灌注好,实验组肝左外叶肿瘤组织可见少许肝动脉供血。肝左外叶门静脉分支结扎(PBL)者均能被DSA证实。结论DSA可直观地显示兔肝动脉与门静脉的空间解剖细节,在兔肝门静脉阻断效果的评价中起着重要作用。     

Atrophy with compensatory hypertrophy of the liver in hepatic neoplasms: radiographic findings

Focal hepatic atrophy has numerous causes and in many cases is associated with compensatory hypertrophy. We have observed this phenomenon on CT in patients with hepatic neoplasms. Of 12 patients studied, eight had hepatic metastases, two had hepatocellular carcinoma, and two had bile-duct carcinoma. Focal changes in liver morphology (i.e., atrophy with compensatory hypertrophy) were found in five patients at presentation and developed after treatment with systemic or intraarterial chemotherapy in the others. Atrophic changes affected the right lobe in eight patients, the left lobe in three, and part of both lobes in one. Compensatory hypertrophy of part or all of the unaffected liver was found. Ten patients had obstruction of the portal vein branch to the atrophic segment, four of these 10 also had hepatic vein obstruction, and two of these 10 also had bile duct obstruction. Portal vein obstruction appears to be the most important element in the production of focal hepatic atrophy in patients with hepatic neoplasms. After treatment with chemotherapy, tumor regression and atrophy may be associated with compensatory hypertrophy and enlargement of the uninvolved part of the liver. This must not be mistaken for progression of disease.