大鼠门静脉转流下耐受入肝血流阻断的安全时限

目的 评估在排除门静脉淤血条件下动物耐受人肝血硫阻断的安全时限。方法 利用大鼠肝脏及肝蒂分支分叶的解剖特点，阻断肝左，中和右叶肝蒂，以尾叶静脉系统作为阻断入肝血流期间门静脉血液的流出道，肝脏复流后切除尾叶，在这一模型上，以阻断入肝血流不同时程后动物7d存活率，肝脏病理组织学改变及肝脏能量代谢功能损害的严重诬蔑工及可逆性来推断动物耐受常温下入肝血流阻断的安全时限。结果 门静脉转流下阻断入肝血流90min以内，术后7d动物全部存活，其肝脏缺血-再灌流损害以肝窦淤血和肝细胞变性等可逆性病变为主，而肝脏能量代谢功能损害可得以代偿和恢复，阻断入肝血流100、110、120min后动物7d存活率分别为50%，30%和20%，肝脏缺血120min后肝脏缺血-再灌流损害则以大量肝组织坏死为显特性，其肝脏能量代谢功能严重受损而陷入失代偿状态。结论 大鼠在门静脉轻流时对常温下持续入肝血流阻断的耐受性显增强。其安全时限是90min。     

大鼠门静脉转流下耐受入肝血流阻断的安全时限

目的 评估在排除门静脉淤血条件下动物耐受入肝血硫阻断的安全时限。方法 利用大鼠肝脏及肝蒂分支分叶的解剖特点,阻断肝左、中和右叶肝蒂,以尾叶静脉系统作为阻断入肝血流期间门静脉血液的流出道,肝脏复流后切除尾叶。在这一模型上,以阻断入肝血流不同时程后动物7d存活率、肝脏病理组织学改变及肝脏能量代谢功能损害的严重度及可逆性来推断动物耐受常温下入肝血流阻断的安全时限。结果 门静脉转流下阻断入肝血流90min以内,术后7d动物全部存活,其肝脏缺血-再灌流损害以肝窦淤血和肝细胞变性等可逆性病变为主,而肝脏能量代谢功能损害可得以代偿和恢复。阻断入肝血流100、110、120min后动物7d存活率分别为50％、30％和20％,肝脏缺血120min后肝脏缺血-再灌流损害则以大量肝组织坏死为显著特性,其肝脏能量代谢功能严重受损而陷入失代偿状态。结论 大鼠在门静脉轻流时对常温下持续入肝血流阻断的耐受性显著增强,其安全时限是90min。     

入肝血流阻断对阻塞性黄疸大鼠肝脏能量代谢的影响

目的 探讨阻塞性黄疸大鼠肝脏缺血后能量代谢变化的病理特征及其与动物耐受性的关系。方法 大鼠胆管结扎后１周,在门静脉转流入阻断入肝血流不同时程后观察动物存活率、肝细胞线粒体呼吸活性、肝组织ＡＴＰ含量及动脉血酮体比值。结果 阻断入肝血流３０、６０及９０分钟后１０天动物存活率分别为１００％、１００％及４０％;缺血后肝脏能量代谢功能明显受损,在再灌注后２４小时,阻断入肝血流３０及６０分钟两组动物肝脏能量代谢功能已有明显恢复,而阻断入肝血流９０分钟组肝脏能量代谢功能仍维持在显著低水平。结论 胆道梗阻后１周,大鼠门静脉转流下入肝血流阻断６０分钟以内肝脏能量代谢功能损害可逆,动物安全耐受;而阻断入肝血流９０分钟引起肝脏能量代谢功能不可逆性损害,动物难以安全耐受。     

门静脉转流下大鼠耐受入肝血流阻断安全时限的实验研究

目的 探讨大鼠常温下耐受人肝血流阻断的最大安全时限。方法 用自行设计的可避免门静脉瘀血的动物模型，通过动物７天存活率、肝脏能量代谢改变的可逆性进行分析。结果 在门静脉转流下，大鼠耐受持续人肝血流阻断的时间显著延长，肝缺血９０分钟恢复灌流后７天，动物全部存活，而缺血１００、１１０、１２０分钟及单纯肝血流阻断３０分钟者存活率分别为５０、３０、２０％及４０％；肝脏能量代谢发迹在血不超过９０分钟者可逆的。     

肝硬变大鼠门静脉转流下耐受入肝血流阻断的安全时限

目的　探讨在门静脉转流条件下肝硬变大鼠耐受入肝血流阻断的安全时限。方法　观测门静脉转流与非门静脉转流条件下阻断入肝血流不同时程后动物存活率及肝脏能量代谢的变化 ,包括肝细胞线粒体呼吸控制率 (RCR)、肝组织三磷酸腺苷 (ATP)含量、动脉血酮体比值 (AKBR)。结果术后两周存活率 :肝硬变大鼠PBB 30min组和PBB 4 5min组为 10 0 % ,PTC 30min组、PBB 6 0min组、PBB 75min组及PBB 90min组分别为 73.3%、75 %、4 6 .7%及 2 6 .7%。正常大鼠PTC 30min组为4 0 %。肝脏能量代谢 :缺血后肝组织ATP、RCR及AKBR均明显下降 (P <0 .0 5 )。再灌注后上述指标逐惭恢复 ,但随缺血时间延长 ,升高幅度明显降低 ,甚至难以恢复。结论　肝硬变大鼠常温下耐受入肝血流阻断的安全时限是 4 5min。     

不同热缺血时间犬自体胰移植物功能状态及存活率的实验研究

目的探讨热缺血时间较长犬胰腺移植物功能和组织形态变化状态,研究不同热缺血时间条件下移植物存活率及供胰耐受热缺血的时限。方法根据供胰热缺血不同时间30、60、90、120 min分组,用UW液保存24 h,然后行自体移植,术后连续观察血糖、静脉葡萄糖耐量试验(IVGTT)、胰液淀粉酶、胰液分泌量、血液中胰岛素含量,并进行病理学检测。结果30 min组和60 min组在术后2~3 d即可恢复至正常范围,而在90 min组和120 min组术后1周血糖不能恢复至正常。IVGTT K值在未热缺血组3、0 min组和60 min组在术后1周>1,而在90 min组和120 min组<1。30 min组和60 min组术后胰液淀粉酶、胰液分泌量、血液中胰岛素含量明显高于90 min组和120 min组(P<0.05)。热缺血30、60、90、120 min各组移植物存活率分别为100%、100%、66.7%、0%。结论移植胰腺经过30~60 min热缺血,UW液保存24 h后移植物生存良好。热缺血时间超过90 min,移植物结构和功能难以恢复,存活率明显降低。     

猪门静脉转流下胰十二指肠切除及肠系膜上静脉-门静脉切除重建的研究

目的 探讨门静脉转流下胰十二指肠切除(PD)及肠系膜上静脉-门静脉(SMPV)切除重建的可行性及安全性,并对其评价。方法 利用猪与人胰腺解剖的相似性,用来模拟人的胰头癌浸润SMPV后的胰十二指肠切除方式,建立门静脉转流下PD及SMPV切除重建的技术及方法。结果 (1)实验组、对照组长期存活率分别为100.0％、66.7％;(2)对照组阻断前后血流动力学参数波动较大,实验组稳定;(3)两组均有肝脏缺血再灌注损伤,但对照组病理损害比实验组重;(4)实验组肠黏膜的病理损害明显轻于对照组;(5)对照组肠黏膜通透性、肠系膜淋巴结肠道菌属培养阳性率及门静脉血内毒素均明显高于实验组。结论 在门静脉转流下,猪胰十二指肠切除联合SMPV切除及自体颈外静脉移植,其操作简便,安全性大,是研究临床手术方式比较实用的技术方法。     

不同热缺血时间对犬胰腺移植物功能及能量代谢状态的影响

目的探讨热缺血时间对胰腺能量代谢状态及胰腺移植后移植物功能的影响。方法切取犬胰腺左叶,按分组要求,胰腺分别经历30、60、90、120min热缺血,以0~4℃UW液灌洗,并保存24h,然后行胰腺节段自体异位移植,同时设正常对照组和未经历热缺血的胰腺节段自体移植组。术后连续观察血糖、静脉葡萄糖耐量试验(IVGTT)、血液中胰岛素含量,测定术后24h和1周时胰液中淀粉酶浓度,高效液相色谱法检测移植前胰腺组织中ATP和腺苷核苷酸总量(TAN),并观察移植后1h时移植物的组织学变化。结果热缺血30min组和60min组的术后3~5d血糖即可恢复至正常范围,而热缺血90min组和120min组术后1周血糖未能恢复至正常;术后1周,无热缺血组、热缺血30min组和60min组的IVGTTK值大于1,热缺血90min组和120min组小于1,且其静脉血中胰岛素的浓度明显低于无热缺血组、热缺血30min组和60min组(P<0.05);热缺血30min组和60min组胰腺组织中ATP和TAN的含量明显高于热缺血90min组和120min组(P<0.05);无热缺血组以及热缺血30min组和60min组的胰腺组织结构基本正常,而热缺血90min组和120min组的组织破坏明显,腺泡坏死、出血和炎症细胞浸润严重。结论用于移植的胰腺热缺血30~60min是安全的,移植后胰腺功能迅速恢复正常;超过60min的热缺血对移植物的能量代谢有显著负面影响。     

热缺血损伤对大鼠移植肝组织能量代谢及存活期的影响

目的：探讨不同热缺血时间下大鼠肝组织能量代谢变化规律,预测供肝耐受热缺血的安全时限。方法：实验动物按供肝热缺血时间分别为0、10、15、20、30、45和60min,随机分为7组。采用反相高效液相色谱法测定单纯热缺血后肝组织能量代谢指标并进行超微结构的观察。然后按各组条件分别作原位肝移植,观察移植后24、48h各组肝组织能量代谢指标的恢复性变化,并统计生存时间。结果：供肝经受热缺血损伤后,肝组织ATP含量和EC水平远逐渐下降,其中前30min下降比较急剧,以后趋向平缓。热缺血30min内肝组织ATP含量和EC水平在肝移植再复流24h后基本得到恢复,术后大鼠仍可以获长期存活。45min组,移植肝在48h后能量代谢的功能也基本恢复,虽不足以影响术后的1周存活率,但对大鼠肝移植术后的3个月存活率影响显著。60min组,肝脏能量代谢储备功能难以恢复,大鼠术后生存天数显著降低。结论：供肝组织三磷酸腺苷（ATP）含量和能荷（EC）水平以及其移植术后恢复的潜能是衡量供肝质量的重要标准。供肝热缺血损伤的时间与肝组织能量代谢功能的恢复及术后动物生存情况密切相关。     

脾静脉-股静脉转流下大鼠全肝缺血再灌注损伤模型的建立

目的建立脾静脉-股静脉转流下大鼠全肝缺血再灌注损伤模型。方法 40只Wistar 大鼠,体重240-270 g,随机分为2组:单纯肝门阻断组(C组);脾静脉-股静脉转流下肝门阻断组(B 组),应用自制转流泵调节转流量在5-10ml·min-1。两组均用无创动脉夹夹闭肝动脉、门静脉及胆总管40min,随后放开动脉夹再灌注。监测缺血前即刻、缺血5、10、40min及再灌注5、20 min时平均动脉压(MAP)、中心静脉压(CVP)、门静脉压(PVP)、心率(HR)、心电图和胃肠淤血情况,观察再灌注1、24 h肝脏、小肠的病理改变及再灌注24 h的存活率。结果与缺血前即刻比较,C组缺血观察40min、再灌注20min时MAP降低,缺血10、40min时CVP降低,再灌注5、20min时CVP升高,缺血5-40 min、再灌注5、20 min时PVP升高,缺血10、40 min、再灌注5、20min时HR升高;B组缺血5-40 min、再灌注5 min时MAP下降,缺血10 min时PVP升高,缺血5 min时HR下降(P<0．05或0．01)。与C组比较,B 组缺血5-40min、再灌注5、20 min时MAP、PVP,缺血10、40min、再灌注5、20 min时CVP,再灌注5、20 min时HR差异有统计学意义,心律失常发生率降低,再灌注24 h存活率升高(P<0．05或0．01)。B组无明显的胃肠淤血。与C组比较,再灌注1 h B组只有少部分肠绒毛顶端有变性脱落,粘膜下炎症不明显,两组肝脏病理均可见肝小叶结构完整,中央静脉及肝窦扩张,汇管区炎症浸润;再灌注24 h时C 组可见肝细胞点片状坏死,B组多为点状肝细胞坏死。结论大鼠脾静脉-股静脉转流下全肝缺血再灌注损伤模型血液动力学稳定,腹腔内脏器无淤血,无肠道屏障破坏。     

The effect of porto-intrahepatic portal bypass on the ischemic liver during clamping the hepatic inflow

The object of this study was to determine the critical bypass flow rate of the porto-intrahepatic portal bypass during clamping the hepatic inflow, and to clarify the pathophysiology caused by this bypass procedure with special emphasis on the hepatic injury. Porto-intrahepatic portal bypass was instituted, using anti-thrombogenic catheter (Anthron), during clamping the hepatic inflow in anesthetized dogs. Bypass flow rate (BFR) was controlled at 10%, 30% and 60% of the portal flow in the individual experimental groups. As the control study, double bypass (portosystemic and femoral arterio-intrahepatic portal bypass) or portal-systemic bypass was instituted during clamping the hepatic inflow, and porto-systemic bypass at 10% and 60% during clamping the portal vein. Total adenine nucleotide (TAN) and adenylate energy charge (EC) of the liver did not change during 2 hour clamp of the portal vein. Clamping the hepatic inflow, unless congested splanchnic circulation, demonstrated the same level as 30% porto-portal bypass. Taking changes in hemodynamics, portal into consideration and arterial pH and PO2 levels, serum transaminase levels, ICG retention rate and animal survival rate, we conclude that insufficient flow rate of porto-portal bypass (10%, 30%) even cause more severe hepatic damage, and critical flow rate must be between 30% and 60% during 1 hour clamp.     

Liver tissue pH measurement can predict survival in rats undergoing normothermic ischemias

The purpose of this study was to evaluate the usefulness of pH measurement of the liver for the prediction of survival after normothermic hepatic ischemia. Liver ischemia was induced in rats with cirrhosis and normal liver by cross-clamping of the portal vein and hepatic artery, bypassing the portal blood to the jugular vein through a shunt tube. The ischemic time periods were selected arbitrarily from 15 to 95 minutes. Preischemic liver function test was assessed by indocyanine green dye. I measured liver tissue pH continuously during the ischemic period. In addition, levels of adenosine triphosphate (ATP) of the hepatic tissue was determined every ten minutes after ischemia by HPLC and energy charge was calculated. There was a significant positive correlation between the postischemic change of the liver tissue pH and that of energy charge. A discriminant analysis yielded an equation predictive of survival: Y = 7.2 *delta pH10 + 27.15 *KICG - 0.07 *ischemic time - (Y greater than or equal to 0; survivors, Y less than 0; nonsurvivors, delta pH10; preischemic pH - pH at 10 minutes after ischemia). The equation predicted survival with 77.8% accuracy. I conclude that liver tissue pH reflects energy charge of the liver during the ischemic period and pH measurement can predict survival with high accuracy in rats undergoing normothermic ischemia.     

原发性肝癌合并门静脉癌栓86例治疗体会

目的探讨肝癌合并门静脉癌栓(PVTT)的有效治疗方法。方法 86例肝癌合并门静脉癌栓患者行肝切除+门静脉取栓+肝动脉、门静脉双灌注化疗栓塞及生物靶向治疗。结果 1年生存率为90%,2年生存率为85%,3年生存率为35%;结论肝切除+门静脉取癌栓+肝动脉、门静脉双灌注化疗栓塞+生物靶向治疗是治疗肝癌合并门静脉癌栓的有效治疗方法。     

门静脉分支结扎后门静脉压力变化与肝再生的关系

目的 探讨90%门静脉分支结扎后大鼠门静脉压力变化与肝再生的关系.方法 45只雄性SD大鼠行90%门静脉分支结扎术,其中5只进行假手术作为对照.观察不同时相点门静脉压力和非结扎侧肝脏质量变化,光学显微镜下观察非结扎侧肝细胞的形态学变化,免疫组织化学方法检测未结扎侧肝细胞的增殖细胞核抗原(PCNA),TUNEL法检测未结扎侧肝细胞的凋亡情况,并进行定最分析.采用Pearson相关分析和t检验分析数据.结果 95%(38/40)的大鼠存活.结扎侧肝叶进行性萎缩,非结扎侧肝叶占全肝质量的比例随时问推移而增加,12 h内增加较缓慢,仅为10.75%;而1～5 d则增加速度明显加快,达到27.57%;7～28 d达到平台期,缓慢增加到32.37%.术前门静脉压力为(9.1±1.8)cm H_2O(1 cm H_2O=0.098 kPa);结扎后立即升高,12 h达到高峰(15.8±2.7)cm H_2O,与术前比较差异有统计学意义(t=6.847,P<0.05);1～28 d由(13.6±2.3)cm H_2O逐渐下降为(9.3±2.0)cm H_2O.术前大鼠PCNA阳性细胞计数为7%±3%,术后12 h至3 d由14%±5%上升至21%±6%,第5天达到高峰为26%±7%,与术前比较差异有统计学意义(t=9.129,P<0.05),随后逐渐恢复正常.TUNEL法检测结果显示,术前大鼠肝脏和术后各时相点大鼠未结扎侧肝脏仅见极少量凋亡细胞.大鼠门静脉压力与非结扎侧肝叶肝细胞PCNA的表达在术后1、3、5 d呈正相关(r=0.913,0.896,0.908,P<0.05),在术后14 d时相点呈负相关(r=-0.926,P<0.05).结论 大鼠90%门静脉分支结扎术后,引起未结扎侧肝细胞的活跃再生,再生后的肝脏可恢复原来的质量;肝再生以肝细胞增殖加速为主,而非肝细胞凋亡减少;门静脉压力变化在肝再生过程中可能发挥重要作用.     

Effect of partial portal vein ligation on hepatic regeneration

To evaluate the effect of portal hypertension and diminished portal venous blood flow to the liver on hepatic regeneration, male rats were subjected to partial portal vein ligation and subsequently to a two-thirds partial hepatectomy. The levels of ornithine decarboxylase activity at 6 h after partial hepatectomy were greater (p less than 0.001) in the rats with prior partial portal vein ligation than in those without portal hypertension. The rats with prior partial portal vein ligation also had greater (p less than 0.005) levels of thymidine kinase activity at 48 h after partial hepatectomy than did those without portal hypertension. Hepatic sex hormone receptor activity was not affected by prior partial portal vein ligation either before or after partial hepatectomy. The reductions in both estrogen and androgen receptor activity observed in the hepatic cytosol after partial hepatectomy were similar to those observed in control animals. These data indicate that animals with portal hypertension having a diminished hepatic portal blood flow have a normal capacity to regenerate hepatic mass following a hepatic resection.     

肝切除时门静脉血部分动脉化的研究

目的 研究犬门静脉血部分动脉化的肝保护作用。方法 建立大保留肝（占全肝６０％）暂时性血流阻断、肝固有动脉切断并切除未阻断肝的急性肝衰模型（对照组）,并行肝总动脉与胃十二指肠静脉吻合（Ａ－Ｐ组）,观察生存率并定时测定丙氨酸转氨酶（ＡＬＴ）、动脉血酮体比（ＡＫＢＲ）及肝动脉脉、门静脉血气分析。结果 对照组７天生存率为３７．５％,Ａ－Ｐ组均较差异有非常显著性（Ｐ〈０．０１）,门静脉和肝静脉血氧分压均较术     

Experimental study on catheter-bypass between superior mesenteric and hepatic hilar portal veins (SMV-HPV bypass)]

Hepatic ischemia is a consequence of concomitant resection of the portal vein and the hepatic artery when it is necessitated in hepatobiliary or pancreatic surgery. We developed an antithrombogenic catheter with a balloon and experimentally evaluated the safety of construction of SMV-HPV bypass using this catheter to simultaneously prevent intestinal vascular congestion and hepatic ischemia. The main portal vein and the hepatic artery were blocked and SMV-HPV shunting was made in five dogs (bypass group); the main portal vein and the hepatic artery were blocked and the SMV was shunted to the femoral vein in others (ischemia group). In the ischemia group, 3 of the 5 dogs died within 5 days, but all animals of the bypass group survived for a long period. In the bypass group, the changes of adenine nucleotide levels, energy charge ratio, liver function, blood coagulation, and fibrinolysis were mild and within physiologic ranges, and none of changes of the hepatic tissue were observed histologically. This bypass procedure is simple and safe to simultaneously prevent hepatic ischemia and intestinal vascular congestion in cases requiring concomitant resection and reconstruction of the portal vein and the hepatic artery.