门静脉营养对大鼠肝切除后肝脏再生的影响

目的 探讨门静脉营养对肝切除后肝脏再生的影响。方法 将Ｗｉｓｔａｒ大鼠４０只随机分为３组：Ⅰ组不手术，自由摄食；Ⅱ组６５％肝切除后用中心静脉营养治疗；Ⅲ组术后门静脉营养治疗。实验第３，６日观察肝脏再生反应。结果 Ⅲ组肝重／体重、肝脏再生率、肝细胞有丝分裂率和ＤＮＡ合成与Ⅱ组比差异有显著意义；Ⅱ，Ⅲ组术后胰岛素水平与Ⅰ组差异无显著意义，而胰高糖素水平明显升高，且Ⅲ组明显高于Ⅱ组，致使Ⅲ组胰岛素／胰高     

冷保存对大鼠部分移植肝再生的影响

目的探讨冷保存对大鼠部分肝移植术后肝再生的影响。方法健康SD大鼠分为Ⅰ组（肝切除组）、Ⅱ组（冷保存1h部分肝移植组）和Ⅲ组（冷保存8h部分肝移植组）。观察各实验组生存率，比较各组术后1、6、12、24、48、72、168h肝质量／体质量比率、肝再生率、有丝分裂指数及增殖细胞核抗原表达。结果Ⅰ、Ⅱ、Ⅲ组7d存活率分别为100％、90％、40％；Ⅲ组术后2～3d大鼠肝质量／体质量比率、肝再生率、有丝分裂指数较Ⅰ、Ⅱ组明显偏低（P〈0．05）；Ⅲ组术后12h内增殖细胞核抗原表达较其余两组明显偏低（P〈0．05），48h才达高峰，至第7天阳性表达仍处高水平。结论长时间冷保存降低了部分肝移植术后的肝再生能力和大鼠术后生存率。     

缺血预处理对肝大部切除术中残肝缺血再灌注损伤的保护作用

目的 观察缺血预处理对大鼠肝大部切除术中残肝缺血再灌注损伤的保护作用。方法 健康的雌性SD大鼠随机分为3组：即单纯肝叶切除组（PH组）、缺血再灌注损伤状态下肝叶切除组（IR组）及缺血预处理组（IP组）。分别取术前及术后0．5、6、12、24、48h等时间点，应用全自动生化分析仪检测血清ALT、AST含量，通过免疫组织化学法检测残肝组织中Ki67和Cyclin D1表达变化，采用放免法检测血清中透明质酸（HA）含量。结果 IP组术后24h内各检测点的AST和ALT值明显高于PH组和IR组（P〈0．05）。术后早期IP组大鼠的血清HA表达量明显高于PH组和IR组（P〈0．05）。PH组大鼠肝细胞Ki67和Cyclin D1表达在术后24h达到峰值，并且明显高于IR组和IP组大鼠（P〈0．05）。其中IP组大鼠术后Ki67和Cyclin D1表达量降低地最显著。结论 在合并肝组织大部缺失时，缺血预处理对残留肝组织的缺血再灌注损伤的保护效应消失，它损害了大鼠残肝再生功能。     

广泛肝切除联合肝固有动脉切除对正常大鼠及梗阻性黄疸大鼠的影响

目的 探索在正常及高胆红素血症情况下,大鼠70%肝切除联合肝固有动脉切除对肝功能、肝细胞能量代谢以及肝再生和细胞凋亡的影响.方法 雄性成年SD大鼠133只,将其中40只分为2组,每组20只,均行胆总管-十二指肠插管桥接,同时行70%肝切除或70%肝切除联合肝固有动脉切除.另87只行胆总管结扎制备梗阻性黄疸模型.5 d后手术分为70%联合肝切除胆肠再通内引流组,及70%肝切除联合肝固有动脉切除、胆肠再通内引流2组.动态观察术后24 h、72 h、7 d肝功能和肝细胞能量代谢、肝组织HGF和bcl-2 mRNA含量及其蛋白表达、肝细胞增殖指数和凋亡指数的变化,并统计各组死亡率.另取6只作为假手术组,测定术后0 h肝功能和肝细胞能量指标.结果 正常大鼠能够耐受70%肝切除联合肝动脉切除,术后肝细胞能量代谢和肝功能迅速恢复正常,肝再生良好.高胆红素血症时,大鼠术后肝再生受抑制,细胞凋亡增多.较之70%肝切除组,70%肝切除联合肝固有动脉切除组对肝细胞能量代谢的影响更为显著,术后肝功能恶化,肝组织HGF和Bcl-2 mRNA含量显著减少,肝再生明显受抑制,细胞凋亡增多,死亡率显著增高(P<0.05).结论 正常大鼠70%肝切除联合肝动脉切除术后肝再生不受影响,高胆红素血症时,70%肝切除联合肝动脉切除的大鼠死亡率高,因此术前引流减黄应是必要的措施.     

保留受者胰腺的肝胰十二指肠器官簇移植一例报告

目的探讨保留受者胰腺的肝胰十二指肠器官簇移植术的方法和疗效。方法2006年9月28日为1例肝移植术后发生胆道并发症合并1型糖尿病的患者实施了肝胰十二指肠器官簇移植，术中采用保留受者胰腺的方法。结果术后1周时，受者肝脏功能基本恢复正常；术后第2天即停用胰岛素静脉泵，移植胰腺功能恢复正常。术后第1天胰尾部出现胰瘘，但引流通畅，未予以其他特殊处理，术后第4天胰瘘自行愈合；术后第4天胃肠功能恢复正常；术后第5天，受者即可自行下床活动。受者现已存活12个月，肝脏和胰腺功能均正常。结论保留受者胰腺的方法不仅简化了器官簇移植术的操作，而且使术中和术后并发症明显减少，从而为需行肝胰十二指肠器官簇移植的良性病受者探索出了一种更为简捷安全的新手术方法。     

肝硬化大鼠部分肝切除后TGF-α和C-met蛋白在肝脏中的表达及其意义

目的：研究转化生长因子－α（TGF－α），C-met蛋白在肝硬化大鼠肝脏中的表达及意义。方法：将成年雄性Wistar大鼠制作为肝硬化大鼠，然后将肝脏部分切除制作肝再生模型。随机分为7组，一组立即处死，计算肝切除率；其他组分别于术后12h,1d,3d,5d,7d,14d处死。用免疫组织化学方法检测TGF－α和C-met蛋白在肝细胞中的表达，以正常大鼠肝再生模型为对照。结果：肝硬化大鼠部分肝脏切除后不同时间肝中TGF－α，C－met蛋白表达的变化均较正常大鼠延迟。结论：TGF－α和C-met在肝脏中的表达显示，硬化肝脏具有再生能力，但较正常肝脏弱。     

肝胰十二指肠器官簇移植外科技术

2004年9月1例原发性肝癌合并胰头转移的患者在我院接受肝胰十二指肠器官簇移植，整块切除全肝、胆囊、十二指肠、胰腺、脾脏、胃大部和部分上段空肠，进行了血管和消化道重建。移植后胰腺功能正常，未应用胰岛素维持。术后第4d肠道功能恢复，术后1周肝功能恢复正常；术后16d时因腹腔内出血行剖腹探查血肿清除术，同时对感染伤口进行减张缝合，愈合良好；术后2月时出现不全性肠梗阻症状，保守治疗后好转。患者目前已存活5个月，肝脏和胰腺功能均正常，痊愈出院。肝胰十二指肠器官簇移植术的成功为上腹部晚期恶性肿瘤患者提供了延长生命的机会，同时为晚期肝病伴有胰腺功能不良患者的彻底治愈探索出新的手术方式。     

围手术期肠内免疫营养对肝硬化肝切除大鼠肝再生的影响

目的：探讨围手术期内使用肠内免疫营养支持对肝硬化肝切除大鼠肝再生功能的影响。方法：48只肝硬化大鼠随机均分为两组。A组为标准肠内营养组，B组为肠内免疫营养组。依标本采集时间的先后， A, B组再各分为4个亚组。两组大鼠用等热量肠内营养剂喂养8d 后行68％肝切除术，术后再喂养至取标本时间。分别于术前、术后1, 4和8d 取相应亚组大鼠肝组织标本，检测肝细胞有丝分裂指数(MI)和增殖细胞核抗原(PCNA)阳性细胞数。结果：两组大鼠肝切除术后残肝表现出一定的再生能力。B组肝细胞MI和PCNA阳性细胞计数在术后4d 和8d 显著高于A组(P<0.05)。结论：围手术期肠内免疫营养支持较之标准肠内营养支持更能增强肝硬化肝切除大鼠残肝再生能力，使肝再生在术后较长时间内保持高水平。     

低氧预适应对大鼠肝切除后残肝组织凋亡相关蛋白表达的影响及意义

目的 观察低氧预适应对大鼠肝切除术后残肝组织凋亡相关蛋白细胞色素C和caspase 3表达的影响及其意义.方法 采用SD大鼠肝切除模型研究低氧预适应对残肝组织凋亡相关蛋白表达的影响及意义.将SD大鼠随机分为对照组(NC组)、单纯肝切除组(HR组)和低氧预适应组+肝切除组(HP组),每组24只.HP组术前用10％氮氧混合气体处理90 min,分别于术后1h、6h、12 h、24 h处死大鼠取肝脏标本,取门静脉血检测肝功能,Western-Blot法测定肝切除大鼠残肝组织细胞色素C和caspase 3蛋白的表达,并在电镜下观察各组肝细胞形态学改变、线粒体损伤程度等.结果 HP组血清ALT和AST水平显著低于HR组,差异有统计学意义(P＜0.05);HP组各时段的肝功能明显优于HR组;HP组各时段细胞色素C和caspase 3蛋白表达明显低于HR组,透射电镜下HR组肝细胞出现典型的凋亡征象,而HP组肝细胞无明显凋亡形态.结论 HP对肝切除后残肝组织的肝细胞凋亡有明显的抑制作用;可能是通过下调细胞色素C和caspase 3蛋白的表达、减轻线粒体损伤途径而发挥其保护作用.     

信号调节蛋白α1在大鼠肝再生过程中表达的实验研究

目的：观察信号调节蛋白α1（SIRPα1）在大鼠肝再生过程中的表达变化。方法：选取雄性SD大鼠120只，随机分为两组：假手术组（SO）和肝切除手术组（OP），每一组又分为10个时间点，即手术后2、6、12、24、30、48、72、120、168和240h，每一时间点6只，切除大鼠70％肝脏（肝左叶和中叶）建立肝再生模型，术后在预定时间点分别取肝组织固定石腊包埋切片，采用免疫组织化学方法测定肝组织SIRPα1表达。结果：再生肝组织12h肝实质可见局灶散在肝细胞膜棕黄色着色，24h弥漫性肝细胞膜着色，120h以后肝细胞膜着色逐渐减弱。结论：SIRPα1作为一种负向调控因子参与了肝细胞再生，可能与肝再生终止有关，但关于其详细调控机制及其与其他因子相互作用的机制有待于进一步研究。     

The effect of denervation on liver regeneration in partially hepatectomized rats

BACKGROUND/AIM: In a partial liver transplantation, the dissected hepatic nerves are left unrepaired during active liver regeneration. In fact, the pathophysiological influence of such hepatic denervation on liver regeneration has not yet been fully clarified. The aim of the present study is to elucidate the effect of total hepatic denervation on liver regeneration. METHODS: Experiment 1: To confirm the effect of hepatic denervation, the hepatic contents of norepinephrine were measured in both denervated (n = 5) and sham (n = 5) rats. The changes in the hepatic microcirculation were also measured in both denervated (n = 5) and sham (n = 5) rats. Experiment 2: The rats (n = 80) were randomly assigned to two groups: DN group (n = 40); hepatic denervation followed by a partial hepatectomy (PH). Control group (n = 40); sham hepatic denervation followed by PH. In both groups, the animals were killed at 12, 24, 36, 48, 72, 120, and 168 h after PH, respectively. The liver to body weight ratio and the proliferating cell nuclear antigen (PCNA) labeling index were measured at each time point. RESULTS: Experiment 1: Nearly a total depletion of norepinephrine (<99%) was observed in the DN rats. In addition, the hepatic tissue blood flow significantly increased in the DN rats. Experiment 2: The liver to body weight ratio of the DN group was also significantly higher than that of the control group at 168 h (P < 0.05). The PCNA labeling index peaked between 24 and 36 h in the control group, while that in the DN group showed a delayed peak. At 72 and 120 h, the PCNA labeling index was significantly higher in the DN group than in the control group (P < 0.05). CONCLUSION: Total hepatic denervation was thus found to enhance liver regeneration after a partial hepatectomy. This phenomenon is partially triggered by the increased hepatic blood flow to the remnant liver.     

HGF和SAM对慢性肝损伤大鼠肝部分切除术后肝细胞的影响

目的:比较肝细胞生长因子（HGF）和S-腺有蛋氨酸（SAM）对大鼠慢性肝损伤时肝部分切除术后肝再生和肝功能的影响,为临床应用提供依据。方法:以四氯化碳和乙醇联合诱导大鼠慢性肝损伤模型,成模后大鼠行30%肝部分切除术,然后随机分为肝硬化对照组,HGF组,SAM组,HGF+SAM组。手术当天起,肝硬化组肌内注生理盐水2 mL/d,HGF组予腹腔注射肝细胞生长因子0.65 mg/（100g·d）,SAM组予肌内注SAM20 mg/（kg·d）,HGF+SAM组同时按上述方法和剂量注射2种药物。各组大鼠分别于术后15d被处死,取血检测AST,ALT,ALB和TB; 同时在光镜及电镜下观察肝组织的病理改变及超微结构变化。结果:HGF组,SAM组,HGF+SAM组术后15 d AST,ALT,TB明显低于肝硬化组(P＜0.05),ALB水平明显高于肝硬化组(P＜0.05); 而HGF组,SAM组,HGF+SAM组3组之间无统计学差异。结论:肝硬化的大鼠肝脏行部分肝切除术后,肝功能及肝储备功能均有一定程度的受损,肝脏再生亦有障碍。HGF和SAM都可促进术后肝细胞再生。     

Possible inhibitory mechanism of liver regeneration through non-parenchymal cells after combined hepatectomy and pancreatectomy

BACKGROUND: Recently, simultaneous hepatectomy (Hx) and pancreaticoduodenectomy have been performed in the treatment of biliary tract cancer. Postoperative hepatic failure is a common and potentially fatal complication. The aim of this study was to examine the reduced rate of liver regeneration after 70% Hx alone or in combination with 70% pancreatectomy (HPx). MATERIALS AND METHODS: Male Sprague-Dawley rats underwent Hx or combined Hx and Px. The ratio of liver-body weight, labeling index of hepatocytes in vivo, and DNA synthesis of hepatocytes and/or Kupffer cells in primary culture were analyzed. RESULTS: The ratio of liver-body weight in HPx rats was found to be significantly lower than that in Hx rats from 12 hours to 72 hours after surgery. There was no difference in blood glucose or ALT levels between the two groups. An inhibitory effect on DNA synthesis was observed in cocultured hepatocytes and Kupffer cells when portal plasma obtained one hour after surgery was added. We further observed that conditioned medium of Kupffer cells stimulated by portal plasma obtained one hour after HPx inhibited DNA synthesis by hepatocytes. This effect was abolished after incubation at 56 degrees C for 30 min. CONCLUSIONS: These results clearly indicate the existence of a growth inhibitory factor in portal serum after HPx. This heat-labile growth inhibitory factor was released from Kupffer cells stimulated by portal plasma after HPx and appears to act on hepatocytes in a paracrine manner.     

小体积肝切除促进肝硬化大鼠模型肝脏再生及肝功能恢复的实验研究

目的 观察小体积肝切除对肝硬化大鼠模型肝脏再生及肝功能恢复的影响.方法 采用CCl4腹腔注射方法制备肝硬化大鼠模型,肝硬化大鼠模型实施20％肝切除(n=30),以肝硬化假手术组(n=30)和正常大鼠20％肝切除组(n=30)作对照.在肝硬化模型制备至20％肝切除术后3个月的过程中,采用苏木精-伊红染色观察肝脏形态结构的变化,定期检测模型肝功能、凝血功能,采用Western blot、Re-al-time PCR检测肝细胞生长因子和转化生长因子-β以及增殖细胞核抗原在肝细胞中的表达情况,并与对照组进行比较.结果 在肝硬化模型制备过程中,苏木精-伊红染色提示大鼠肝脏逐渐呈现肝纤维化、肝硬化样改变;与正常大鼠比较,肝硬化动物模型中转化生长因子-β基因、蛋白表达逐渐增强.在接受20％肝切除术后3个月,肝硬化模型肝功能及凝血功能均较术前有所改善,同时TGF-β表达水平显著低于作为对照的肝硬化假手术组(P＜0.05),而肝细胞生长因子和增殖细胞核抗原基因、蛋白表达水平显著高于作为对照的肝硬化假手术组(P＜0.05).结论 小体积肝切除有助于促进肝硬化大鼠模型肝脏再生及肝功能的恢复,这为进一步深入开展小体积肝切除防治肝硬化进展的相关研究提供了新思路.     

Is parenchyma-preserving hepatectomy a noble option in the surgical treatment for high-risk patients with hilar bile duct cancer?

BACKGROUND: The essential minimum of hepatic segmentectomy combined with caudate lobectomy (parenchyma-preserving hepatectomy) has been recommended particularly for high-risk patients with hilar bile duct cancer to minimize the risk of postoperative liver failure. This quality control study investigated whether parenchyma-preserving hepatectomy is a "noble option" in the surgical treatment of hilar bile duct cancer. PATIENTS AND METHODS: A total of 53 patients with hilar bile duct cancer underwent surgical resection. These patients were retrospectively classified into a major hepatectomy group (major Hx, n=30), a parenchyma-preserving hepatectomy group (preserving Hx, n=11), and a hilar bile duct resection group (HBDR, n=12). A preserving Hx consisted of caudate lobectomy, either alone (n=3), or combined with resection of segment 4 (S4, n=4), or S58 (n=3) or S458 (n=1). The preserving Hx was used for high-risk patients in whom tumor tissue was diagnosed to be Bismuth type I and II by preoperative selective percutaneous transhepatic cholangiography. RESULTS: The mean numbers of hepatico-jejunostomies were 2.8, 4.8, and 4.6 in the respective groups. Mortality rates including hospital death were 13.3%, 0%, and 0% respectively. Morbidity rates were 46.7%, 54.5%, and 33.3%. The preserving Hx group encountered no liver failure (T.Bil>10 mg/dl, encephalopathy) but acquired hyperbilirubinemia (T.Bil>5 mg/dl), pulmonary insufficiency and other complications at the same frequency as in the major Hx group. The survival rates in the three groups were 35.6%, 52.5%, and 48.6% at 3 years and 25.2%, 14.9%, and 24.3% at 5 years respectively. Curability rates (R0 to R1+2) were 76.7%, 54.5% and 50.0%, respectively. Preserving Hx tended to result in higher frequencies of positive transmural margins (e.g., cancer cells remaining around the right hepatic artery or the portal vein). CONCLUSIONS: Preserving hepatectomy for high-risk patients should be limited strictly to patients who do not have tumors which are not invading adjacent organs (e.g., T2) nor a segmental duct and are confined longitudinally to the right or the left.     

Abdominal wall repair is delayed during hepatic regeneration

BACKGROUND: Abdominal wall wound failure remains a common surgical problem. The signals that activate normal fibroplastic repair versus regeneration pathways are unknown. Transforming growth factor beta levels rise during incisional healing but fall during hepatic regeneration. Changes in the injured host cytokine milieu may therefore differentially effect abdominal wall repair versus hepatic regeneration. MATERIALS AND METHODS: Forty-eight rats were divided into four groups (n = 12). Groups 1-3 underwent sham celiotomy, 70% hepatectomy, or 80% enterectomy with anastamosis. Incisions from Group 4 were treated with either 1 microg of transforming growth factor beta(2) (TGF-beta(2)) or vehicle following hepatectomy. Isolated fascial and dermal incisions were harvested and tested for breaking strength on POD 7. Serum (TGF-beta(2)) and hepatocyte growth factor (HGF) levels were measured by ELISA. RESULTS: Recovery of incisional wound breaking strength was delayed following hepatectomy but not enterectomy (P<0.002). The inhibitory effect was observed in both the fascia and the dermis of the abdominal wall. TGF-beta(2) levels were depressed in hepatectomy animals on POD 7, while at the same time HGF levels were elevated. Exogenous TGF-beta(2) shifted the healing trajectory of deficient wounds back toward a control pattern. CONCLUSION: Abdominal wall fascial and dermal healing is delayed during hepatic regeneration. Elevated HGF and depressed TGF-beta(2) suggest a host mechanism that prioritizes hepatic parenchymal regeneration over fibroplastic repair (scar). Observations such as these are needed as therapeutic wound healing enters the clinical realm.     

肝切除联合肝动脉切除对梗阻性黄疸大鼠肝细胞再生和凋亡的影响

目的 探索在梗阻性黄疸时,不同范围肝切除联合肝动脉切除对肝细胞再生和凋亡的影响.方法 155只雄性SD大鼠行胆总管结扎制备梗阻性黄疽模型,5 d后二次手术分为:胆肠再通内引流组;肝切除(42%、70%)联合胆肠再通内引流组;肝切除(42%,70%)联合肝固有动脉切除、胆肠再通内引流组.动态观察二次手术后24 h、72 h、7 d肝组织HGF、bcl-2 mRNA含量及蛋白表达、肝细胞增殖和凋亡指数的变化,并统计各组死亡率.结果 高胆红素血症、行胆肠冉通内引流的同时,大鼠肝切除或肝切除联合肝动脉切除后,肝再生均受抑制,凋亡增多;较之肝切除组和42%肝切除联合肝固有动脉切除组.70%肝切除联合肝固有动脉切除组术后肝组织HGF、bcl-2 mRNA含量显著减少,肝细胞再生明显受抑而凋亡显著增多,死亡率显著增高(P<0.05).结论 高胆红素血症时,肝切除量是影响大鼠肝切除联合肝动脉切除实施安全性的重要因素,42%肝切除联合肝固有动脉切除、胆肠再通内引流,对肝细胞再生和凋亡影响较小,安全町行;70%肝切除联合肝动脉切除、胆肠再通内引流后肝细胞再生显著受抑制,凋亡增多,死亡率高,应避免实施.