甲氰咪胍对肝硬变门静脉高压症患者门静脉压力影响的初步观察

肝硬变时血中组织胺等液递物质含量增加,并促使门静脉压力(PVP)升高。本文观察了组织胺受体拮抗剂甲氰咪胍对肝硬变门静脉高压症患者PVP的影响,发现经周围静脉一次快速推注甲氨咪胍0.2g使肝硬变门静脉高压症患者的PVP平均下降0.42kpa,其中4例下降幅度达0.49～0.69kpa。PVP的下降幅度与血清白蛋白浓度呈高度负相关(r=-0.76;P<0.05)。肝组织学检查发现,PVP下降幅度较大的患者其肝细胞变性坏死也较严重。对照组(非肝硬变患者)给予甲氰咪胍后PVP无明显变化。本文结果说明通过拮抗肝硬变时血中某些异常升高的液递物质,可以达到降低PVP的目的。     

一氧化氮在肝前性门静脉高压症形成中的作用

目的：了解一氧化氮（NO）在肝前性门静脉高压症形成中的作用。方法：部分门静脉结扎（PVL）法制备肝前性门静脉高压症大鼠模型，以硝酸还原酶和比色法检测正常组，假手术（SO）组及PVL组术后不同时间点的门静脉血浆NO、一氧化氮合酶（NOS）水平，观察其血流动力学指标的动态变化及NOS抑制剂硝基－L－精氨酸甲酯(L-NAME)对门静脉高压大鼠血流动力学的影响。结果：SO组各时间点与正常组比较，NO，NOS及血流动力学指标均无显性差异，PVL组术后各时间点与正常组比较，NO，NOS，门静脉压力（PVP），门静脉阻力（PVR）明显升高（P＜0．05），平均动脉压（MAP），内脏血管阻力（SVR）明显降低（P＜0．05），门静脉血流量（PVF）无显性差异，且血浆NO水平与PVP，PVF，SVR，MAP呈显相关性，NAME能使门静脉高压大鼠PVP，PVR显下降（P＜0．05），使SVR，MAP显上升（P＜0．05）。结论：门静脉高压症大鼠存在高动力循环状态；NO参与了PVL术后血流动力学的变化及肝前性门静脉高压症模型的形成。     

缬沙坦对肝硬化门静脉高压大鼠胃黏膜微循环及超微结构的影响

目的观察缬沙坦降低大鼠肝硬化门静脉高压（PHT）的疗效和对胃黏膜微循环及其超微结构的影响。方法制作肝硬化PHT模型，成模后分为模型组、缬沙坦组及正常对照组，治疗1513后进行各指标的测定。结果与模型组比较，缬沙坦组门静脉压力（PVP）明显降低（P〈0.01），光镜下胃黏膜微循环明显改善，毛细血管最大直径及面积明显减小（P〈0．01），透射电镜下胃黏膜超微结构的损伤也明显减轻，而平均动脉压（MAP）和心率（HR）无明显变化。结论缬沙坦可有效降低大鼠肝硬化PVP，对门静脉高压性胃病（PHG）有明显的治疗作用。     

Changes of blood humoral substances in experimental cirrhosis and their effects on portal hemodynamics

The changes of humoral substances in the blood of cirrhotic rats were studied together with their effects on portal hemodynamics at different stages during the development of cirrhosis. The profiles of humoral substances and hemodynamics in two different cirrhotic rat models were also investigated. During the development of cirrhosis, glucagon increased markedly in all stages, histamine and vasoactive intestinal polypeptide (VIP) increased in the early stage, serotonin (5-HT) and somatostatin (SS) increased in the middle and late stages. There were different patterns of humoral substances in different cirrhotic models. Glucagon was the main humoral substance elevated in CCL4 induced cirrhosis, but histamine and 5-HT were mainly elevated in the blood in thioacetamide (TAA) induced cirrhosis. The hemodynamics altered differently in different stages during the development of cirrhosis and differently in the two cirrhotic rat models. Exchange transfusions between normal and cirrhotic rats resulted in an elevation of portal flow in normal rats, but no such changes were found after exchange pressure and an increase of portal blood transfusions between normal rats. The relationship between the humoral substances and portal hemodynamics is discussed. The results of this study strongly support the hypothesis of "humoral mechanism" in the pathogenesis of portal hypertension due to cirrhosis.

     

门脉局部注入DDPH治疗大鼠肝硬化门脉高压的实验研究

目的 研究l—(2，6—二甲基苯氧基)—2—(3，4—二甲氧基苯乙氨基)丙烷盐酸盐(DDPH)对实验性大鼠肝硬化门脉高压症的治疗作用，探讨合适的药物及给药途径。方法 在CCl4诱发的大鼠肝硬化门脉高压模型上，分别经下腔静脉或门静脉注入哌唑嗪(PRZ)，维拉帕米(VER)和DDPH，测量门静脉压(PVP)、下腔静脉压(ICVP)、平均动脉压(MAP)和心率(HR)，比较两种给药途径对门脉和全身血流动力学影响的特点，并观察DDPH对肝纤维化的防治作用。结果 门脉注入DDPH使PVP、MAP下降，并呈剂量依赖性，PRZ随剂量增加降PVP、MAP作用呈逐渐减弱的趋势，VER降PVP、MAP作用最弱，减慢HR作用最强。DDPH门脉给药后PVP下降，50min时仍无明显恢复，其它2种药物停止注药后PVP开始恢复，50min时降压作用基本消失；3种药物门脉给药降PVP作用明显强于下腔静脉给药，降MAP作用则明显弱于后者，对HR影响均较小；DDPH可以减轻CCl4对肝细胞的损害和肝纤维化的程度。结论 DDPH是理想的治疗肝硬化门脉高压症的扩血管药物，门脉是扩血管药物治疗门脉高压症的理想途径。     

Effect of cimetidine on wedged hepatic venous pressure in cirrhotic patients

According to our supposition that "humoral mechanism" plays an important role in the pathogenesis of portal hypertension due to cirrhosis, antagonists to some of humoral substances would lower the portal pressure in cirrhotic patients. Wedged hepatic venous pressure (WHVP) was used as an indicator for changes of portal pressure. Cimetidine was given intravenously to 8 cirrhotic patients, in whom an average lowering of 0.72 kPa (7.3 cm H2O) of WHVP was observed subsequently. This change was of clinical significance as compared with the previous results of splenorenal shunting operations.

     

Effects of hepatotrophic factors on the liver after portacaval shunt in rats with portal hypertension

Background Portacaval shunt （PCS） prevent hepatotrophic factors from flowing into the liver, but they enter directly the systemic circulation and worsen liver injury. This study was designed to investigate the effects of hepatotrophic factors through the portal vein on the liver in rats with portal hypertension after portacaval shunt. Methods Intrahepatic portal hypertension （IHPH） was induced by intragastric administration of carbon tetrachloride, and end-to-side PCS was performed. Eight normal rats served as controls, and eight rats with IHPH served as IHPH model （IHPH group）. Another 32 rats with IHPH-PCS were randomly subdivided into 4 groups： normal saline （NS） given to 8 rats, hepatocyte growth factor （HGF） 8, insulin （INS） 8, hepatocyte growth factor and insulin （HGF＋INS） 8. Hepatotrophic factors were infused into the portal vein through an intravenous catheter. Portal venous pressure （PVP） was measured. The levels of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were tested biochemically and those of hyaluronic acid （HA） and laminin （LN） were measured by radioimmunoassay. Hepatic fibrosis was assessed histologically and the expression of collagens type I and In were detected immunohistochemically. Ultrastructural change of hepatocytes and the number of mitochondria were observed under an electron microscope. The data were compared between groups and subgroups by Student-Newman-Keuls procedure with SPSS 10.0. Results PVP was significantly higher in the IHPH rats than in the control rats （P〈0.05）. The levels of serum ALT, AST, HA, and LN, hepatic fibrosis score, the amount of collagen deposition, collagens type I and III increased more significantly in the IHPH group than in the control rats （P〈0.05）. The number of mitochondria decreased more significantly in the IHPH rats than in the control rats （P〈0.05）. The levels of serum ALT, AST, HA and LN as well as hepatic fibrosis score, the amount of collagen deposition, and the amount of collagens type I and M in the HGF and HGF＋INS rats were significantly lower than those in the NS rats （P〈0.05）. The damage to hepatocyte ultrastructure was markedly alleviated and the number of mitochondria was increased more significantly in the HGF and HGF＋INS rats than in the NS rats under an electron microscope. Conclusions Perfusion of exogenous hepatotrophic factors through the portal vein can alleviate liver injury, minimize the damage to the ultrastructure of hepatocyte, protect liver function, and lessen hepatic fibrosis in rats with portal hypertension after PCS.     

PACS手术和传统SRS、PCDV手术治疗门脉高压症的比较

目的:对丝线栓塞性门脉高压模型犬进行PACS手术和传统SRS手术、PCDV手术,分别观察不同术式对门静脉血流动力学的影响。方法:制备门脉高压动物模型;PCDV组实施脾切除、贲门周围血管离断术;SRS组实施脾切除,远端脾肾分流术。PACS组实施脾切除、门静脉-脾动脉吻合、门静脉-腔静脉吻合。彩色多普勒超声测量手术前后的入肝门脉血流、压力、入下腔门脉血流、压力;门静脉、肠系膜上静脉的内径、最大血流速度、血流方向、门静脉侧支循环和血栓形成情况,术中动态测量门静脉压(PVP)。结果:PCDV组术后门静脉流量(PVF)下降17%,PVP下降5%,门静脉血栓发生率为37%;SRS组术后PVF下降51%,PVP下降50%;PACS术后向肝PVF上升至原来的180%,向肝PVP上升至原来的196%,门静脉入下腔门脉血流量增至原来的130%,门静脉入下腔门脉压力保持低压,约为原来的45.5%,相对于传统手术SRS或PCDV的门脉PVF和PVP治疗结果均具有极为显著的统计学差异(P<0.05,P<0.01)。结论:PCDV术后门静脉高压瘀血状态并无明显改善,胃粘膜瘀血加重,复发曲张静脉破裂出血的威胁依然存在;SRS术后PVF减少和PVP均有显著性下降,门静脉血流量进一步减少,肝脏血供术后仍然受到很大影响;PACS手术成功率较高,手术死亡率等同SRS手术,可同时提高入肝血流和降低侧支压力,是一种值得尝试和进一步研究的新手术方法。     

特立加压素和垂体后叶素对肝硬化大鼠门脉压力及胃粘膜血流量的影响

为探讨特立加压素和垂体后叶素对肝硬化大鼠门脉压力、平均动脉压及胃粘膜血流量的影响，采用美国BIOPAC公司生产的MP100型多导生理记录仪测定肝硬化大鼠门脉压力和胃粘膜血流量，并观察给予特立加压素和垂体后叶素前后门压力及胃粘膜血流量的变化。发现特立加压素和垂体后叶素均可显著降低肝硬化大鼠门脉压力及胃粘膜血流量，但特立加压素对动脉压力的影响较垂体后叶素小，且降低胃粘膜血流量的速度快，结果表明特立加压素对于降低肝硬化门脉高压较垂体后叶素为优，对门脉高压性胃病的治疗具有一定的疗效。     

多层螺旋CT肝脏灌注预测肝硬化门静脉高压并上消化道出血风险性价值

目的 探究多层螺旋CT肝脏灌注预测肝硬化门静脉高压并上消化道出血风险性价值。方法 对笔者医院肝硬化门静脉高压者进行研究,其中未出血者31例,出血者21例,另选取30例体检正常者作为对照组,所有研究对象均进行CT灌注成像。对比3组肝动脉灌注量（HAP）、门静脉灌注量（PVP）、肝脏总灌注量（THP）、肝动脉灌注指数（HPI）以及静脉内径参数：门静脉直径（PVD）、脾静脉直径（SVD）、肠系膜上静脉直径（SMVD）、胃冠状静脉直径（GCVD）水平,统计脾门-胃底静脉血管截面数量、血管总面积,创建受试者工作特征曲线（ROC）,对比不同指标曲线下面积（AUC）。结果 与对照组比较,肝硬化门静脉高压患者PVP、THP降低,HPI升高,出血组变化程度高于未升高组;与对照组比较,肝硬化门静脉高压患者PVD、SVD、SMVD、GCVD水平以及血管截面数量、血管总面积均升高,且出血组静脉内径变化程度高于未出血组,差异均有统计学意义（P<0.05）。Logistic多因素回归分析显示,GCVD、血管截面数量、血管面积与上消化道出血发生具有显著相关性（OR=1.398,OR=1.427,OR=1.394）,差异有统计学意义（P<0.05）。ROC曲线显示血管面积AUC值（0.826）高于GCVD、血管截面数量（0.702、0.768）,预测价值最高。结论 GCVD、血管截面数量、血管面积均能够预测肝硬化门静脉高压并上消化道出血,其中静脉血管面积预测价值最高。