不同性别肝大部切除小鼠的肝再生

背景:各种病因所致的肝硬化及肝癌发病率存在明显的性别差异.肝受损或手术后肝脏均可通过其自身强大的再生能力进行代偿,但肝再生过程中不同性别肝细胞的再生状况是否存在差异尚不清楚.目的:比较肝大部切除后不同性别小鼠肝脏再生能力是否存在差别.方法:采用不同性别成年昆明小鼠行肝脏大部切除,称量手术切除的肝组织,并于术后1,3,5,7,10,14 d取再生肝组织,称量后常规制作组织切片备用,取材前2 h腹膜下注射5一溴脱氧尿核苷50 mg/kg.观察比较不同性别小鼠再生肝组织的结构变化、细胞形态,以及术后各时间点肝再生率、肝组织5一溴脱氧尿核苷的标记指数.结果与结论:苏木精一伊红染色切片镜下结果显示,肝脏大部切除后各时间点不同性别小鼠肝组织结构无明显差别.不同性别小鼠肝大部切除后各时间点肝再生率及5一溴脱氧尿核苷标记指数差异均无显著性意义(P>0.05).提示肝大部切除后不同性别小鼠肝的再生能力无明显差别.     

部分肝切除大鼠不同时期肝再生组织中转化生长因子β1的表达

背景:肝部分切除的安全性高低依赖于余肝的再生能力,了解肝硬化情况下肝部分切除后的肝再生情况,对肝硬化患者的治疗及预后具有重要意义.目的:探讨转化生长因子β1在肝硬化大鼠肝部分切除后肝组织中的表达和意义.方法:正常组大鼠不施加任何干预因素,模型组大鼠建立肝硬化模型,实验组大鼠建立肝硬化模型后行肝部分切除,复制肝再生模型.运用免疫组织化学方法和Western blotting技术,检测各组肝部分切除后12,24,72h肝组织中转化生长因子β1的表达.结果与结论:与模型组比较,实验组术后12,24 h肝组织转化生长因子β1的表达无明显差异(P0.05),术后72 h肝组织中转化牛长因子β1的表达显著增强(P<0.01).提示硬化肿部分切除后早期转化生长因子β1表达无明显增加,主要从中晚期可能通过与其他细胞因子的相互作用,继而开始发挥调节肝再生的功能.     

大鼠肝部分切除后肝细胞再生及肝星状细胞α-平滑肌肌动蛋白表达变化与肝细胞生长因子的干预作用

背景:肝细胞的再生主要受细胞因子的整体控制,肝细胞生长因子在肝细胞的再生过程中发挥着重要的作用,但其对肝星状细胞再生替代的研究较少.目的:观察肝细胞生长因子对大鼠肝部分切除后肝细胞再生及肝星状细胞α-平滑肌肌动蛋白表达的影响.设计、时间及地点:随机对照动物实验,于2006-11/2007-05在河南省组织再生重点实验室完成.材料:选用健康SD雌性大鼠52只,体质量(200±20)g,用于制造肝切除动物模型.肝细胞生长因子由北京生物药业有限公司提供.方法:将52只大鼠按随机数字表法分为3组,假手术组(n=12)打开腹腔,重新关腹.术后第2天腹腔注射生理盐水1 mL/d;肝部分切除组(n=20)行肝部分切除,术后第2天腹腔注射生理盐水1 mL/d;肝细胞生长因子组(n=20)肝部分切除术后第2天腹腔注射肝细胞生长因子12mg/(kg·d),1次,d.主要观察指标:各组分别于术后第1,2周末采血行血清学检测;取肝组织行苏木精-伊红及α-平滑肌肌动蛋白免疫组化染色,并行电镜观察.结果:52只大鼠全部进入结果分析.①与假手术组相比,术后第1周肝部分切除组血清谷丙转氨酶、谷草转氨酶活性升高,总蛋白含量降低,肝再生指数降低(P＜0.05),肝细胞生长因子组上述指标明显改善(P＜0.05).②术后第1,2周各组肝组织α-平滑肌肌动蛋白表达灰度值相近.③术后第1周肝细胞生长因子组肝细胞内的粗面内质网、线粒体均明显增多.第2周后各组肝细胞超微结构无明显差异.结论:应用外源性肝细胞生长因子可以改善大鼠肝部分切除后的肝功能,促进肝细胞增殖,但在肝部分切除术后2周内对肝星状细胞无明显影响.     

肝细胞生长因子对慢性肝损伤时肝部分切除术后肝再生和肝功能的影响

目的研究肝细胞生长因子对慢性肝损伤时肝部分切除术后肝再生和肝功能的影响。方法对慢性肝损伤模型SD大鼠行30%肝部分切除术,术后10d,经腹腔注射肝细胞生长因子,同时建立正常对照组。观察不同剂量肝细胞生长因子对肝再生,肝功能和肝储备功能的影响。结果实验组与对照组相比,AST,ALT,总胆固醇、动脉血酮体比具有显著的统计学意义(P<0.01)。结论应用外源性肝细胞生长因子可明显改善肝功能和肝储备功能,促进肝细胞再生。     

肝部分切除病人手术前后护理

对38例肝癌病人行肝部分切除术治疗的术前术后护理,术前做好有针对性的心理护理,评估心、肺、肝、肾功能,做好皮肤、肠道等术前准备工作,术后复苏期严密监测生命体征,严格做好各种管道的护理,密切观察有无出血、肝功能衰竭、胆瘘、膈下感染和胸腔积液、肺部感染等并发症,并做好相应并发症的护理,可有效降低病死率,减少并发症发生率。     

Pure laparoscopic hepatectomy for hepatocellular carcinoma patients with severe liver cirrhosis

Hepatocellular carcinoma often arises in cirrhotic livers. Patients with severe liver cirrhosis who undergo hepatectomy often develop postoperative liver failure, even if the hepatectomy is limited. Here, we report six patients with severe liver cirrhosis (Child-Pugh B/C and indocyanine green retention rate at 15 min ≥ 40%) who underwent pure laparoscopic hepatectomy. Their perioperative course was favorable and comparable to that of other hepatocellular carcinoma patients with mild-moderate liver cirrhosis. In patients with severe liver cirrhosis, pure laparoscopic hepatectomy minimizes the disturbance in collateral blood and lymphatic flow caused by laparotomy and liver mobilization, as well as the mesenchymal injury caused by compression of the liver. It limits complications such as massive ascites, which can lead to severe postoperative liver failure. Good candidates for the procedure include patients with severe liver cirrhosis who have tumors on the liver surface and in whom adaptation to ablation therapy is difficult and/or who experience local recurrence after repeat treatments.     

30例肝癌患者肝切除后断面的处理

目的 总结30例刮吸法断肝术中断面处理的手术经验。方法 1999年6月至今 ,30例肝癌患者行刮吸解剖法断肝 ,肝创面内直径≤2.0mm肝静脉 ,≤1mm的Glisson管系可直接电凝 ,口径>2mm的肝静脉及>1mm的Glisson管系分别结扎。结果 本组30例 ,无围手术期死亡 ,各种并发症发生情况 ,1例膈下积液 ,2例右胸腔积液 ,无手术后出血 ,无胆漏 ,并发症发生明显减少。结论刮吸法解剖法行肝切除 ,有助于减少肝切除术后并发症的发生     

Molecular events associated with accelerated proliferative response in rat livers when partial hepatectomy is preceded by a sham operation

BACKGROUND: When a sham operation is performed 6 h before partial hepatectomy (PH), the regenerative response is accelerated suggesting that sham operation itself contributes to cellular events leading to proliferation. MATERIALS AND METHODS: In order to examine the mechanisms implicated in this acceleration, we compared the activation of several factors associated with the progression through the cell cycle at various times after PH and after PH preceded by sham operation (S6 h + PH). The effect of a single sham (S) and two combined sham operations (S6 h + S) was also examined. Nonoperated rats were used as controls (C). RESULTS: The early factors NF-kappaB and Stat3 were activated after S6 h + PH and S6 h + S. C-jun expression was increased 0.5 h and 2 h after PH and 6 h after sham. There was no further increase in S6 h + PH and S6 h + S. In contrast, c-myc expression returned to baseline levels after S6 h and a new increase was observed 2 h after S6 h + PH but not after S6 h + S. P53 mRNA was significantly expressed 6 h after S6 h + PH, but at a level similar than that observed 6 and 12 h after PH alone. An earlier increase in c-Ha-ras mRNA and cyclin E protein was found in S6 h + PH, in comparison with PH alone. CONCLUSIONS: The first divergent response between the two combined models involved c-myc expression. However, major differences related to the accelerated liver regenerative response observed after S6 h + PH were found at late time points associating an earlier expression of c-Ha-ras and nuclear cyclin E.     

Hepatic regeneration and metabolism after partial hepatectomy in normal rats: effects of insulin therapy

The effect of insulin therapy on liver regeneration has been studied in normal fed rats 12, 24 and 48 h after partial hepatectomy. Dry weight of regenerating liver increased between 12 and 48 h after partial hepatectomy and was unaffected by insulin therapy. [6-3H] Thymidine uptake peaked at 24-h (24.7 +/- 2.4% of total liver cells) and insulin treatment had no additional effect. At 12-h after partial hepatectomy, hepatic [ATP] was decreased 15%, while [ADP] and [AMP] were increased 47% and 83% respectively compared with sham-operated animals. Partial hepatectomy also caused an increase in hepatic [triglyceride], a decrease in hepatic [glycogen] and an increase in the levels of glucose and several glycolytic intermediates. The hepatic redox ratios, [lactate]:[pyruvate] and [3-hydroxybutyrate]:[acetoacetate], were elevated. Insulin therapy had only minor effects on hepatic adenine nucleotide levels, intermediary metabolite concentrations or intrahepatic redox ratios after partial hepatectomy. These findings suggest a decreased hepatic intracellular energy state in regenerating liver; insulin therapy in normal rats does not influence this metabolic change nor the regenerative response.     

老年患者行选择性右肝切除术后的肝功能评价

目的评价≥65岁老年患者行选择性右肝切除术后的肝功能情况。方法采用回顾性研究,分析行选择性右肝切除术（Ⅴ～Ⅷ段）的24例≥65岁老年患者和22例≤40岁患者的病历资料,统计两组患者的手术死亡、术后并发症和肝功能情况。结果≥65岁老年患者组手术死亡1人,术后严重并发症发生率为12.50％;而≤40岁患者组无手术死亡,术后严重并发症发生率为5.00％,两组手术死亡情况比较,差异无统计学意义（χ2=1.00,P＞0.05）,两组的严重并发症发生率经Fisher精确概率法检验,差异亦无统计学意义（P＞0.05）。≥65岁老年患者组需要术中或术后输血8例多于≤40岁患者组6例,但差异无统计学意义（χ2=0.20,P＞0.05）,且两组红细胞使用单位数及住院时间比较,差异均亦无统计学意义（t分别=1.04、1.32,P均＞0.05）。两组肝功能变化情况：术后在术后第2天内凝血酶原时间（PT）和总胆红素（TBS）指标变化最明显,PT明显下降,TBS明显上升;术后2～5 d变化缓慢,待术后第5天, PT明显上升,TBS缓慢下降,趋于术前水平。天冬氨酸转氨酶（AST）在术后第2天内迅速上升至最高点,γ谷氨酰胺转肽酶（GGT）缓慢下降至最低点;从第2天开始,AST逐渐下降,GGT缓慢上升至术前水平。丙氨酸转氨酶（ALT）与AST变化趋势一致,碱性磷酸酶（ALP）与GGT变化趋势一致。两组患者变化趋势基本一致。结论≥65岁老年患者行选择性右肝切除术后的肝功能情况与年轻患者（≤40岁）无明显差别。     

肝部分切除大鼠内毒素血症与再生肝结构功能的动态比较

目的探讨肝部分切除大鼠内毒素血症与再生肝组织结构以及功能的动态变化规律及其意义。方法102只健康雄性成年Wistar大鼠随机分为正常对照(NC)组、假手术(SO)组和肝部分切除(PH)组,在不同时间点检测循环血内毒素(ET)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、白蛋白(ALB)、结合胆红素(CB)与透明质酸(HA)水平以及肝组织病理学改变。结果血清ET在PH术后6~72h期间升高,在12h、48h呈现峰值,分别与NC组比较(P<0.05,P<0.01);血清ET在SO组各时间点与NC组比较差异无显著性。血清ALT在PH组术后6~72h期间升高,与血清ET动态变化趋势比较呈正相关(r=0.817,P<0.01);血清AST在PH组术后6~48h期间升高,与血清ET动态变化趋势比较呈正相关(r=0.717,P<0.05);血清ALB在PH组术后6~72h期间下降,与血清ET动态变化趋势比较呈负相关(r=-0.790,P<0.05);血清CB在PH组术后6~48h期间升高,与血清ET动态变化趋势比较呈正相关(r=0.836,P<0.01);血清HA在PH组术后6~72h期间升高,与血清ET动态变化趋势比较呈正相关(r=0.849,P<0.01);上述肝功能各指标在SO组各时间点与NC组比较差异均无显著性。再生肝组织出现损伤的时间段与血清ET升高的时间段(6~72h)一致,肝细胞坏死明显的时间点与血清ET出现峰值的时间点(12h,48h)一致;SO组各时间点肝组织与NC组肝组织比较无显著差异。结论PH后产生的内毒素血症可能直接造成再生肝组织结构与功能损伤,但这种损伤在数天内可自行完全恢复。提示对健康机体施行肝部分切除获取供肝是安全的。     

Portal vein infusion of cancer chemotherapeutic agent emulsified with Lipiodol in regenerating liver after partial hepatectomy in rats

Portal vein infusion of aclarubicin (ACR) emulsified with Lipiodol (LP) in regenerating liver after 70% partial hepatectomy in rats was evaluated for its safety and usefulness. DNA synthesis in regenerating liver was transiently suppressed by LP, ACR or LP+ACR, but no obvious inhibition was seen in aminopyrineN-demethylase activity and liver weights. LP significantly enhanced hepatic tissue levels of ACR and its active metabolites by long-term retention in the sinusoidal space. This study demonstrates that in rats LP has a powerful effect on the long-term retention of anticancer agents in the sinusoidal space after infusion into the portal vein, without aggravating hepatic damage by anticancer agents.