前列腺素E1对大鼠肝脏缺血再灌注损伤的保护作用

目的 探讨前列腺素E1（PGE1）对肝脏 因再灌注损伤的保护作用。方法 制作常温下大鼠部分肝叶缺血再灌注模型，于缺血前经门静脉给予PGE1，45min后恢复血流灌注，并于1h后取门静脉血测定血清谷草转氨酶（GOT）、谷丙转氨酶（GPT）、乳酸脱氢酶（LDH）、肿瘤坏死因子－α（TNF－α）及内皮素1（ET－1），同时取缺血肝叶行病理组织学检查。结果 缺血再灌注组GOT、GPT、LDH及TNF－α和ET－1均明显高于正常对照组，PGE1组则明显低于缺血再灌注组。PGE1组的肝脏病理组织学改变明显轻于缺血再灌注组，并接近正常对照组。结论 PGE1对肝缺血再灌注具有保护作用。     

山莨菪碱对肝脏缺血再灌注损伤的保护作用

目的 探讨山莨菪碱对肝脏缺血再灌注损伤的保护作用。方法 将雄性Wistar大鼠制成肝脏缺血再灌注模型，随机分为正常对照组、缺血再灌注组、生理盐水组和山莨菪碱组，观察肝脏缺血60min再灌注1、3、6、12及24h后血浆和／或肝组织中内皮素－1（ET－1）、透明质酸（HA）、丙氨酸转氨酶（ALT）、丙二醛（MDA）和再灌注1h后肝细胞内游离Ca^2 ([Ca^2 ]i)、ATP含量变化以及肝组织病理学改变。结果 肝脏缺血再灌注后血浆和／或肝细胞中ET－1、HA、ALT、MDA和肝细胞内[Ca^2 ]u含量均显著升高，而肝组织中ATP含量明显降低；肝脏缺血再灌注前应用山莨菪碱2.0mg/kg者，血浆HA和肝细胞内[Ca^2 ]i含量明显降低，肝组织中MDA也有不同程度的降低，而肝组织中ATP含量明显升高，同时肝酶的漏出减少，肝组织病理学损害明显减轻。结论 山莨菪碱对肝脏缺血再灌注损伤具有保护作用。     

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。     

肝细胞凋亡与肝移植中热缺血损伤关系的实验研究

目的：探讨肝细胞凋亡是否参与肝移植中热缺血再灌注这一病理损伤过程。方法：实验以大鼠供肝获取前供体所经历的心脏停搏时间0、30和60min将实验动物分为3组：HB组、NHBD－30组和NHBD－60组，而后行大鼠原位肝移植，每组各20对。于术后1、3、6和24h处死取材。移植肝标本采用HE染色、TUNEL技术和透射电镜进行观察，并采集血样以测定TNF－α。结果：HB组几乎未出现肝细胞凋亡。移植术后3－6h，NHBD－30组出现了少量肝细胞凋亡，而NHBD－60组则出现了大量肝细胞凋亡。移植术后24h，NHBD－30组和NHBD－60组则分别出现了局灶性和大片肝细胞坏死。随着供肝遭遇的热缺血时间不断延长，术后TNF－α呈上升趋势，在术后3h达到峰值。结论：肝细胞凋亡参与肝移植中热缺血再灌注损伤，肝细胞凋亡可能是坏死的原因，并且肝细胞凋亡与TNF－α表达关系密切。     

选择性胆管栓塞所致肝脏功能及组织学变化的实验研究

目的通过动物实验研究,观察选择性胆管栓塞所致肝脏功能和组织学变化,探讨其治疗胆管细胞癌的可能性。方法应用无水酒精或α-氰基丙烯酸正辛酯(DTH胶)对新西兰兔行选择性胆管栓塞,与正常新西兰兔比较,进行大体、组织学观察,并检测肝脏功能变化。结果栓塞术后30 d被栓塞肝叶萎缩,体积减小,质地变硬,光镜下肝小叶结构消失,肝细胞消亡,汇管区结缔组织增生明显。未栓塞肝叶代偿性肥大,肝细胞体积及密度增大,门静脉扩张充血。肝功能呈一过性改变,表现为术后3 d转氨酶(GPT、GOT)明显升高,术后14 d降至正常基线水平。DTH胶对肝功能(GPT、GOT)的损害要轻于无水酒精组(F=9.593,P=0.015;F=16.401,P=0.004)。结论选择性胆管栓塞可使被栓塞肝叶明显萎缩、纤维化,而未栓塞肝叶代偿性增生肥大,DTH胶栓塞效果较无水酒精相对安全有效,可能作为胆管细胞癌治疗的一种辅助措施。     

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.     

常温肝缺血再灌注损伤的实验研究

目的：探讨肝缺血再灌注损伤的作用机制。方法：采用大鼠部分肝缺血再灌注模型，将健康雄性SD大鼠24只随机分为三组：A组（手术对照），B组（肝缺血90min），C组（肝缺血90min再灌注120min）。观察每一动物肝组织病理切片；分别检测血浆谷草转氨酶（AST）、谷丙转氨酶（ALT）、乳酸脱氢酶（LDH）、肿瘤坏死因子（TNF－α）、白介素1β（IL-1β）浓度；测定肝组织中髓过氧化物酶（MPO）含量。结果：肝缺血再灌注后，光镜下大鼠肝组织有明显的肝血窦和中央静脉瘀血，内皮细胞及肝细胞普遍水肿变性；C组肝细胞坏死较B组明显；血浆中肝功能酶学指标显著升高，（B、C组与A组比及C组比B组P均＜0．01）；肝组织中MPO活性升高，以再灌注120min组为著（C组比A组P＜0．01）；与血浆中TNF－α、IL-1β的变化趋势相同（TNF－α：C组比A组P＜0．05，IL－1β：B、C组比A组P均＜0．01）。结论：肝脏微循环障碍是肝缺血再灌注损伤的病理基础；TNF－α、IL-1β介导中性粒细胞参与的肝缺血再灌注损伤过程。     

参附注射液对大鼠肢体缺血再灌注后肝脏损伤的保护作用

目的观察参附注射液对大鼠肢体缺血再灌注损伤后肝功能、血红素加氧酶-1（HO-1）表达的影响,并对其保护机制做一初步探讨。方法 64只清洁级SD雄性大鼠,用随机数字表法随机分为4组,每组16只,分别为假手术组、缺血再灌注组、参附干预组、参附＋锌原卟啉Ⅸ（Znpp）干预组。假手术组：大鼠麻醉后仅分离不夹闭股动脉,分离血管前10 min以7.5 mL/kg腹腔注射生理盐水;缺血再灌注组：夹闭股动脉前10 min以7.5 mL/kg腹腔注射生理盐水,夹闭股动脉缺血3 h,再灌注4 h;参附干预组：夹闭股动脉前10 min以7.5 mL/kg腹腔注射参附注射液,夹闭股动脉缺血3 h,再灌注4 h;参附＋Znpp干预组：术前30 min腹腔注射Znpp 5 mg/kg,余同参附干预组。再灌注完毕后取材,取外周静脉血测血清谷丙转氨酶（GPT）、谷草转氨酶（GOT）含量;取肝组织测定肝组织中丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性;采用免疫组织化学法测定肝脏组织中HO-1蛋白表达;光镜下观察肝脏病理学改变。结果 1与假手术组比较,各肢体缺血再灌注造模组MDA含量均明显升高（P〈0.05）,SOD活性明显降低（除参附干预组外,P〈0.05）,GPT、GOT含量均明显升高（P〈0.05）,HO-1蛋白表达明显升高（P〈0.05）。2与缺血再灌注组比较,参附干预组MDA含量明显降低（P〈0.05）,SOD活性明显升高（P〈0.05）,血清GPT、GOT含量明显降低（P〈0.05）,肝组织中HO-1蛋白表达升高（P〈0.05）。3与参附干预组比较,参附＋Znpp干预组MDA含量明显升高（P〈0.05）,SOD活性明显降低（P〈0.05）,血清GPT、GOT含量明显升高（P〈0.05）,而肝组织HO-1蛋白表达差异无统计学意义（P〉0.05）。结论肢体缺血再灌注可造成肝脏功能损伤,给予参附注射液预处理可以减轻肝脏损害程度,这种保护作用可能与参附注射液预处理上调HO-1蛋白在肝组织中的表达、抑制氧自由基生成?     

大鼠肝、胰十二指肠联合切除残肝肝细胞生长因子表达的研究

目的 用实验动物模型同时切除肝脏、胰腺及十二指肠，以探讨肝细胞生长因子(HGF)对残肝再生的影响。方法 60只SD大鼠被随机分为4组：①68％肝切除组；②68％肝叶切除加50％胰腺切除组；③68％肝叶切除加十二指肠切除组；④68％肝叶切除、加50％胰腺切除加近端十二指肠切除组。每组中3只大鼠分别于术后12、24、48、72和168h处死并采集肝脏样本，计算肝再生率。切除的肝脏组织用RT-PCR技术检测HGF在术后不同时间的表达，并与免疫组化法检测的肝细胞增殖细胞核抗原(PCNA)进行对比研究。结果 68％肝切除组残肝HGF的表达逐渐增强，24h达到高峰，随后逐渐下降，168h时达最低水平。而肝、胰切除，肝十二指肠切除和肝、胰十二指肠切除可显著减少残肝细胞HGF的表达，并使HGF的表达延迟至术后48h。结论 HGF可促进肝脏切除术后残肝的再生反应，而起源于胰腺和十二指肠外分泌腺的其他因素亦对HGF的表达起显著的调节作用，从而影响肝细胞的增殖。     

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目的探讨临床上施行复杂的肝脏部分切除手术前,增加肝细胞内糖原含量能否减轻术中因阻断肝血流所带来的肝脏缺血-再灌注损伤及其相关机制.方法将近3年收治的临床基本情况相近的17例病人分为实验组及对照组.实验组于术前24h内静脉滴注25%葡萄糖250mL,共4次(每6h1次);对照组不作特殊处理.两组病人均采用阻断第一肝门方法行病变肝脏切除术.术中分别于肝脏缺血前、缺血后及再灌注1h,获取相对正常的肝组织测定组织中ATP含量及肝细胞膜Na     

Lack of protection of ischaemic preconditioning in the rat model of major hepatectomy with ischaemia reperfusion injury

OBJECTIVE: To investigate the effects of ischaemic preconditioning (IP) on residual liver regeneration after major hepatectomy without portal blood bypass in rats, and to verify whether it can protect the residual liver from ischaemia reperfusion (IR) injury. METHODS: Ninety rats were randomized into three groups: Group PH, rats were subjected to 70% hepatectomy alone; Group IR, rats were subjected to 30 minutes of total hepatic ischaemia, and 70% hepatectomy was performed just before reperfusion; Group IP, rats were pretreated with IP (5/10 minutes). During the preoperative period and at 0.5, 6, 12, 24 and 48 hours after the operation, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured using an autoanalyser. Serum hyaluronic acid (HA) was measured by radioimmunoassay. Regenerated liver weight (RLW) of the rats was measured and the expressions of Ki-67 and cyclin D1 were determined by immunohistochemistry in remnant liver tissue. RESULTS: There were no significant differences in serum AST and ALT levels in all the groups before the operation. After partial hepatectomy, AST and ALT levels increased rapidly. From 0.5 to 24 hours after operation, serum AST and ALT levels were significantly higher in IP group rats than in PH and IR rats (p < 0.05). There were no significant differences in serum HA levels in all the groups before the operation. After partial hepatectomy, HA levels increased rapidly, reaching peak values at 12 hours. In the early stage (during 12 hours) after the operation, HA level was significantly higher in IP rats than in PH and IR rats (p < 0.05). The RLW of the rats rapidly increased after partial hepatectomy, and significantly decreased in IP rats compared with PH and IR rats (p < 0.05). Cyclin D1 and Ki-67 expression in all groups before the operation were low and were not significantly different. After partial hepatectomy, they rapidly increased. The expression of Ki-67 and cyclin D1 reached a peak at 24 hours after the operation in PH rats, and they were significantly higher compared with IR and IP rats (p < 0.05). In groups IR and IP, the expression of cyclin D1 and Ki-67 reached peak values at 48 hours. A significant decrease (p < 0.05) was observed after 24 and 48 hours of reperfusion in group IP compared with groups PH and IR. CONCLUSION: IP impairs residual liver regeneration after major hepatectomy without portal blood bypass in rats, and protection from IR injury disappears. IP-induced hyperperfusion may be the cause of reduced liver regeneration.     

Cobalt-protoporphyrin induced heme oxygenase overexpression and its impact on liver regeneration

Cobalt-protoporphyrin (CoPP)-dependent induction of heme oxygenase (HO)-1 has been shown to protect from ischemia-reperfusion injury, which remains a major source of graft loss after liver transplantation. The impact of HO-1 on liver regeneration, especially in reduced-size grafts, has not yet been evaluated. Using an experimental model, we investigated HO-1 induction by CoPP treatment on postoperative recovery of ischemically injured livers following partial (70%) hepatectomy. Wistar rats underwent partial hepatectomy under temporary inflow occlusion (30 minutes). One group of animals received CoPP (5 mg/kg body weight i.p.) 24 hours prior to surgery to induce high levels of HO-1 at the time of surgery, and the second group served as nontreated controls. At postoperative days 1, 4, 7, and 10, animals were exsanguinated, and blood and liver samples were stored for enzymatic (serum AST and ALT levels) and histologic (mitotic index) analyses (n = 5 each day). Additionally, postoperative body weight and weight of the remnant liver were measured. Although serum AST and ALT levels as well as remnant liver weight were comparable between both groups, CoPP-treated animals recovered from surgery more quickly as indicated by postoperative body weight. Moreover, the number of mitotic cells was significantly increased in this group at day 1 (33 +/- 5 versus 20 +/- 5 per 2000 hepatocytes) as compared with nontreated animals. Liver regeneration of ischemically injured livers following partial hepatectomy was improved by HO-1 overexpression following preoperative CoPP administration. Thus, it is conceivable that prevention of ischemia-reperfusion injury by HO-1 overexpression also might be beneficial for reduced-size liver grafts without affecting their proliferative capacity.     

Gadolinium pretreatment decreases survival and impairs liver regeneration after partial hepatectomy under ischemia/reperfusion in rats

BACKGROUND: Modulation of Kupffer cell functions by treatment with gadolinium chloride protects the liver against reperfusion injury. However, its effect on liver regeneration after hepatectomy under ischemia/reperfusion has not been studied. Using a common clinical ischemia/reperfusion technique, we examined the effect of gadolinium on liver regeneration after hepatectomy in rats. METHODS: After an initial 15-minute ischemia and 15-minute reperfusion, 70% hepatectomy was performed during the second 15-minute ischemia period in gadolinium-pretreated (gadolinium group) and saline solution--pretreated (control group) rats. The 24-hour survival rate, relative liver weight, DNA synthesis rate, and hepatic adenosine triphosphate level were examined immediately after hepatectomy and on postoperative days (PODs) 1, 2, 3, and 7. Serum levels of total bilirubin, glutamic pyruvic transaminase, and endotoxin were also measured. RESULTS: The 24-hour survival rate was significantly lower in the gadolinium group (67%) than in the control group (100%). On POD 1, the relative liver weight and DNA synthesis rate were significantly lower in the gadolinium group than in the control group. On POD 1, serum total bilirubin and endotoxin levels were significantly higher in the gadolinium group than in the control group. Immediately after hepatectomy, the hepatic adenosine triphosphate level was significantly lower in the gadolinium group than in the control group. CONCLUSIONS: Under ischemia/reperfusion, gadolinium pretreatment impairs liver regeneration and energy status after hepatectomy and decreases postoperative survival.     

Effect of Short-term Administration of Prostaglandin E<Subscript>1 </Subscript>on Viability after Ischemia/Reperfusion Injury with Extended Hepatectomy in Cirrhotic Rat Liver

The cytoprotective effect of prostaglandin E₁ (PGE₁) has been demonstrated experimentally and clinically against hepatic ischemia and reperfusion injury and against the effects of partial hepatectomy in both individual and combined models of noncirrhotic livers. Cirrhotic livers are more vulnerable to ischemia/reperfusion injury during hepatectomy than are noncirrhotic livers, and postoperative malfunctioning complicates life with multiple organ failure. Cirrhotic livers with tumors have mostly been treated conservatively because extended hepatectomy with induced ischemia during surgery is impossible. The purpose of our study was to document postoperative surgical adaptation in inoperable cases with improved survival after extended hepatectomy in a rat model of cirrhosis treated by PGE₁. Cirrhosis was induced by intraperitoneal injections of 1% dimethylnitrosamine. The liver was subjected to 15 minutes of total ischemia by occluding the hepatoduodenal ligament. Hepatectomy was performed during ischemia. Pretreatment with PGE₁ (0.4 g/kg/min) (or without it in the controls) was given for 15 minutes by intravenous infusion prior to inducing ischemia and during reperfusion. Portal venous flow (PVF) and liver tissue blood flow (LTBF) were measured during reperfusion. At the end of 60 minutes of reperfusion, venous blood was collected for liver function tests. The animals were followed up regarding survival for 48 hours. The PVF and LTBF were significantly improved in the PGE₁ group. The blood chemical analysis indicated that PGE₁ significantly suppressed posthepatectomy liver dysfunction. Most importantly, PGE₁ treatment markedly improved the survival rate, from 42% in the controls to 75% in the test animals at 24 hours after hepatectomy and from 17% in the controls to 58% in the test animals at 48 hours. We concluded that short-term administration of PGE₁ makes extensive hepatectomy possible under ischemic conditions in cirrhotic livers.     

冷缺血对大鼠小体积肝移植肝再生的影响

目的探讨冷缺血对大鼠小体积肝移植术后肝再生的影响.方法本组在2002年9月～2004年8月利用大鼠肝总量30%原位肝移植模型,实验分为肝总量70%肝切除组(C组)和冷缺血1、3、5 h组(E1、E2、E3组),观察1w生存率及肝重量/受体原肝重量比值(EGW/RLW),并检测术后1、2、3、7d肝细胞增殖活性及肝组织学变化.结果E1组1w生存率及EGW/RLW分别达100%和95%,均明显高于E2、E3组(P均＜0.05);E1、E 、E3组均于术后2d达到增殖高峰,其中E1组峰值显著高于E2、E3组(P＜0.001),且与C组峰值无差异(P＞0.05);组织学检查见E1组肝细胞核分裂明显活跃.结论冷缺血1 h的小体积供肝和70%肝切除后肝脏具有同样的增殖活性,仅增殖高峰稍晚;冷缺血超过3h严重影响小体积供肝的再生能力和受者的存活率.     

FR167653 improves survival and pulmonary injury after partial hepatectomy under ischemia/reperfusion in rats.

BACKGROUND: FR167653 is a potent suppressant of production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta, which play an important role in hepatic and pulmonary injury due to ischemia/reperfusion of the liver and in liver regeneration after hepatectomy. We examined the effects of FR167653 on hepatectomy under ischemia/reperfusion in rats. METHODS: After initial 15-min ischemia and 5-min reperfusion, 70% hepatectomy was performed during the second 15-min ischemia period in FR167653-treated (FR group) and saline-treated (saline group) rats. The survival rate, relative liver weight, TNF-alpha, IL-1 beta, DNA synthesis rate of the remnant liver, and histological change and adhesion molecule (ICAM-1) of the lung were examined. Serum glutamic pyruvic transaminase and hepatic malondialdehyde were also measured. RESULTS: Expressions of TNF-alpha and IL-1 beta in the remnant liver were significantly inhibited in the FR group compared to the saline group. The survival was significantly better and pulmonary damage was less in the FR group after hepatectomy under ischemia/reperfusion. ICAM-1 expression of the lung was not altered after hepatectomy and was not significantly different between the two groups. Liver regeneration and injury were not significantly different between the two groups. CONCLUSION: FR167653 does not affect liver injury and regeneration after hepatectomy under ischemia/reperfusion, while it ameliorates pulmonary injury and improves the survival.     

Increased intraabdominal pressure impairs liver regeneration after partial hepatectomy in rats

BACKGROUND: There are many experimental studies showing that increased intraabdominal pressure (IAP) reduces liver blood flow, leading to ischemia and portal venous congestion. But, there is no study evaluating the effect of increased IAP on liver regeneration. It is well known that acute liver ischemia and portal venous congestion impair liver regeneration. We, therefore, aimed to determine the effect of increased IAP on liver regeneration in this study. METHODS: Sprague-Dawley rats underwent partial hepatectomy with or without IAP of 12-14 mm Hg for 24 h or sham operation. Rats were randomly divided into six groups: two sham-operated groups, two hepatectomy groups, and two hepatectomy with increased IAP groups. Mitotic index, proliferating cell nuclear antigen (PCNA)-labeling index, and liver regeneration rate as liver regeneration parameters were studied on day 1 or on day 4 after operation. Additionally, serum aspartate transaminase (AST) level and histopathological changes in intestinal mucosa were studied. RESULTS: Hepatectomy with/without increased IAP groups had significantly higher serum AST levels than the sham-operated group on day 1. Serum AST level was found to be significantly higher in the hepatectomy with increased IAP group than in the other groups on day 4. Intestinal mucosal injury was found in the hepatectomy with increased IAP groups on days 1 and 4. Mitotic index and PCNA-labeling index were markedly higher in all hepatectomy with/without increased IAP groups than in the sham-operated groups. However, together with liver regeneration rate, both indices were significantly less in the hepatectomy with increased IAP groups than in the hepatectomy groups both on day 1 and on day 4. CONCLUSION: Maintenance of IAP between 12 and 14 mm Hg for 24 h impaired liver regeneration after partial hepatectomy in rats.     

Experimental study on tumor growth in the regenerating liver

The purpose of this study was to investigate the effect of liver regeneration on the growth of liver tumor. VX2 carcinoma was transplanted in the liver of New Zealand white rabbits, and 40% partial hepatectomy was performed. The following results were obtained. 1. After 40% partial hepatectomy VX2 carcinoma was transplanted in the remaining liver. Two weeks later, the tumor volume was larger in partially hepatectomized than in shamoperated rabbits (p less than 0.01). 2. When 40% hepatectomy of rabbits which carrying VX2 carcinoma transplanted 2 weeks previously was performed, the mitotic index of the tumor at 24 to 36 hours was significantly higher in hepatectomized than in sham-operated rabbits (p less than 0.02). At 24, 36, 48 hours after partial hepatectomy, the mitotic index of the hepatocytes of the hepatectomized group was significantly higher than that of sham-operated group (24 hrs.: p less than 0.005, 36 hrs.: p less than 0.01, 48 hrs.: p less than 0.005). 3. At 36 hours after partial hepatectomy there was a significant increase of DNA synthesis in tumor cells as compared with that in sham-operated controls (p less than 0.05). These data indicate that liver regeneration enhances the tumor growth in regenerating liver.     

21例原发性肝癌患者术后死亡原因分析

本文总结了我科自1988年以来手术后围手术期死亡的21例原发性肝癌患者,男性18例,女性3例。其中肝癌主瘤位于右肝13例,左肝3例,肝门部1例,中肝(即左内和右前叶)4例。肿瘤平均直径为9cm,最大者为14cm。21例患者均有不同程度的肝硬变。手术方式以肝叶部分切除术为主。患者死亡相对集中的时间为术后7天内、术后7~14天和术后14天以后。同时分析了术后不同时间患者死亡的原因,并就肝叶切除量与肝衰及肝硬变与肝再生的关系进行了探讨。     

Effects of ischemic preconditioning on regenerative capacity of hepatocyte in the ischemically damaged rat livers

BACKGROUND: Liver regeneration after partial hepatectomy is regulated by several factors that activate or inhibit hepatocyte proliferation. A short period of ischemia-reperfusion (IR), called ischemic preconditioning (IPC), protects the liver against subsequent sustained ischemic insults. The present study investigated the effects of IPC on liver regeneration after partial hepatectomy under IR in rats. MATERIALS AND METHODS: Male Wistar rats were subjected to 45 min of total hepatic ischemia, and 70% hepatectomy was performed just before reperfusion. Animals were pre-treated with either IPC (10/15 min) (IPC + PHx group) or not (ischemia + PHx). The survival rate, serum transaminases, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 levels, hepatocyte proliferation and histological change of the remnant liver were measured in both groups and compared with non-ischemic controls subjected to 70% hepatectomy alone (PHx group). RESULTS: The survival rate was significantly better in the IPC + PHx group than in the ischemia + PHx group. Furthermore, IPC reduced liver injury determined by liver histology and serum transaminases. There was an early rise in serum TNF-alpha and IL-6 levels in the ischemia + PHx group. Compared with non-ischemic controls, IPC significantly decreased TNF-alpha, but not IL-6 during the late (24 and 48 h) phases of reperfusion. Rats subjected to 70% hepatectomy and 45 min of hepatic ischemia showed significantly reduced hepatocyte proliferation (mitotic index, proliferating cell nuclear antigen, and relative liver weight) when compared with animals subjected to hepatectomy alone. However, hepatocyte proliferation was markedly increased in rats pretreatment with IPC when compared with ischemic controls. CONCLUSION: These results suggest that ischemic pre-conditioning ameliorates the hepatic injury associated with ischemia-reperfusion and has a stimulatory effect on liver cell regeneration that may make it valuable as a hepatoprotective modality. Il-6 appears to be key mediator in promoting regeneration after combined ischemia and hepatic resection.