门静脉高压症大鼠断流术后胃黏膜缺氧诱导因子-1α和血管内皮生长因子的表达

目的 观察缺氧诱导因子-1α（HIF-1α）和血管内皮生长因子（VEGF）在断流术前后肝前性门静脉高压症（PHPH）大鼠胃黏膜的表达，探讨HIF-1α和VEGF在门静脉高压胃病（PHG）的发生发展的作用。方法 取Wistar大鼠制备PHPH模型80只，设假手术组（SO）60只，在术后3周施断流术。检测HIF-1α、VEGF和CD34在大鼠胃壁组织中的表达。结果 断流术前PHPH组大鼠胃壁中HIF-1α（5．8±1．3）和VEGF（12．0±3．0）的表达均明显高于SO组[HIF-1α（0．03750±0．05175），VEGF（0．7±0．1），P〈0．01]。术后HIF-1α、VEGF和MVD均有升高趋势。结论 HIF-1α和VEGF可能参与了PHG的发生发展，断流术本身能通过某种机制影响HIF-1α和VEGF的表达，加重PHG。     

门静脉高压症食管胃底曲张静脉破裂出血的紧急手术处理

食管胃底曲张静脉破裂大出血（简称大出血）是门静脉高压症的一个常见和严重并发症：国外资料表明大约30％的肝硬变门静脉高压症患者在其疾病进程中会发生大出血,如未经有效的治疗,病人1年内再出血率高达70％,2年内则为100％。国内资料表明,门静脉高压症患者约有50％会发生静脉曲张破裂出血,再次出血的死亡率可达58％。近年来由于诊疗技术的进步,对门静脉高压症大出血抢救成功率有了很大提高,其死亡率显著下降,我院资料显示本世纪70年代以前门静脉高压症患者首次出血死亡率为60％,80年代降到41％,1995到1997年内科统计首次出血死亡率为19．3％。     

缺氧诱导因子-1α、血管内皮生长因子在兔早期肝硬化形成过程中的表达

目的 观察兔早期肝硬化形成过程中缺氧诱导因子(HIF)-α、血管内皮生长因子(VEGF)在肝组织的表达.方法 实验设四氯化碳诱导和正常对照组各15只新西兰大白兔,分别每2周处死实验组3只,正常对照组3只,同时进行常规病理学检测及免疫组织化学检测.结果 HIF-α免疫组织化学染色阳性细胞主要位于肝细胞的细胞质中,部分细胞核中也有表达.VEGF免疫组织化学染色阳性细胞位于肝细胞的细胞质、细胞核和血管内皮细胞中.HIF-1α、VEGF阳性表达均呈棕黄色颗粒.HIF-1α、VEGF在早期肝硬化期(12周末)阳性表达数均为10例;在肝纤维化期(8周末)阳性表达数均为9例;在肝炎期(4周末)阳性表达数均为4例.HIF-1α mRNA、VEGF mRNA在3个时期表达水平差异有统计学意义(P＜0.05),并随时间延长其阳性表达率增加.结论 通过对兔早期肝硬化形成过程中HIF-1α、VEGF在肝组织的表达的观察,为临床基因靶点治疗肝脏疾病提供实验基础.     

HIF-1α与VEGF在皮肤恶性黑色素瘤中的表达

目的 探讨缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)与血管内皮生长因子(vascular endothelial growth factor,VEGF)在恶性黑色素瘤组织中的表达及其相关性.方法 采用免疫组织化学方法研究HIF-1α与VEGF分别在32例恶性黑色素瘤标本与11例健康皮肤标本组织中的表达.结果 32例恶性黑色素瘤中HIF-1α的阳性表达率为62.5%(20/32),VEGF的阳性表达率为84.8%(27/32);11例健康皮肤组织中HIF-1α的阳性表达率为9.1%(1/11),VEGF的阳性表达率为18.2%(2/11).健康皮肤组与恶性黑色素瘤组间比较,HIF-1α与VEGF的表达差异有统计学意义,且恶性黑色素瘤组的HIF-1α与VEGF的表达呈正相关(P<0.05).结论 ①HIF-1α、VEGF在恶性黑色素瘤中呈高表达,提示其可能参与了恶性黑色素瘤的发生和发展.②HIF-1α、VEGF在恶性黑色素瘤组的表达呈正相关,提示恶性黑色素瘤中的HIF-1α可能参与了对VEGF的调控.     

缺氧诱导因子-1α在腹主动脉瘤中的表达及其意义

目的　观察缺氧诱导因子 (HIF) 1α信号传导途径在腹主动脉瘤 (AAA)中的表达 ,探讨AAA的发病机制。方法　选取AAA标本 2 2例 ,以 5例正常腹主动脉 (NA )标本作对照。采用Northern杂交、Western蛋白印迹及免疫组织化学方法检测HIF 1α的mRNA及蛋白产物表达 ,Western蛋白印迹和免疫组织化学方法检测血管内皮生长因子 (VEGF)的表达 ,免疫组织化学抗CD3 4染色法检测微血管密度 (MVD)。结果　AAA组织中HIF 1α的mRNA及蛋白产物表达明显高于NA(P <0 .0 1) ;VEGF表达亦明显增强 (P <0 .0 1) ,与HIF 1α表达呈显著正相关 (r值为0 .783 ,P <0 .0 1)。HIF 1α表达主要分布在AAA中层血管平滑肌细胞 (VSMC)及外膜处 ,与VEGF的分布部位基本一致。AAA中微血管密度明显增加 (P <0 .0 1) )。结论　HIF 1α在AAA发病过程中可能发挥重要作用 ,其作用机制可能是通过促进VEGF的表达而实现的。     

缺氧诱导因子-1α与血管内皮生长因子在肝硬化、肝癌组织中的相关性研究

目的　观察肝硬化、肝癌组织中缺氧诱导因子 (HIF) 1α的表达以及和血管内皮生长因子 (VEGF)相关性。方法　对 14 6例手术切除后的肝硬化和肝癌标本进行连续切片和免疫组织化学检测 ,比较同一组织细胞中HIF 1α表达的临床病理意义 ,并分析HIF 1α和VEGF表达的相关性。结果　HIF 1α普遍表达在肝硬化、肝癌组织中 ;较来源的肝硬化组织而言 ,肝癌组织中HIF 1α的表达显著下调 (P <0 .0 5 )并与组织分化程度有关 (P <0 .0 5 ) ,与癌栓形成、预后无关 (P >0 .0 5 ) ;HIF 1α与VEGF在肝硬化、肝癌组织中的表达显著相关 (r =0 .92 3 ,P <0 .0 5 )。结论　肝硬化、肝癌组织中VEGF的表达依赖于HIF 1α ;肝细胞癌变后缺氧程度减轻。     

缺氧诱导因子-1α与血管内皮生长因子在胶质瘤中的表达

目的 探讨缺氧诱导因子（HIF）-1α与血管内皮生长因子（VEGF）在不同级别胶质瘤中的表达特点及其生物学特性。方法 采用逆转录-聚合酶链反应（RT-PCR）法和免疫组织化学法分别检测20例新鲜冷冻标本及117例多聚甲醛固定的不同级别胶质瘤标本中HIF-1α与VEGF的表达情况，并对实验结果进行半定量计算和统计学分析。结果 RT-PCR结果示正常脑组织和Ⅰ-Ⅳ级胶质瘤中HIF-1αmRNA平均吸光度值分别为11．99、12．18、48．31、80．96、112．77，正常脑组织和Ⅰ级胶质瘤间差异元统计学意义，其余各组间差异均有统计学意义（F=969．45，P〈0．01）；而VEGF mRNA平均吸光度值分别为29．50、37．97、60．33、84．61、112．97，各组间差异均有统计学意义（F=312．91，P〈0．01）。免疫组织化学结果示HIF-1α在正常脑组织和Ⅰ-Ⅳ级胶质瘤中的阳性表达率分别为10％、13．3％、53．5％、80．6％、100％，正常脑组织和Ⅰ级胶质瘤间差异无统计学意义，其余各组间差异均有统计学意义（χ^2=38．19，P〈0．05）；同样，VEGF在各组中的阳性表达率分别为0％、33．3％、62．8％、83．3％、100％，各组问差异均有统计学意义（χ^2=45．78，P〈0．05）。结论 HIF-1α与VEGF在胶质瘤中的表达与胶质瘤的病理分级密切相关，随着病理级别的升高，HIF-1α与VEGF无论是在mRNA水平还是在蛋白水平的表达均上调，并且两者间的表达也具有相关性。     

血管内皮生长因子参与门静脉高压症内脏高动力循环

目的 检测血管内皮生长因子(vascular endothelial growth factor,VEGF)在门静脉高压症(portal hypertension,PHT)内脏血管中的表达变化,探讨其在内脏高动力循环中的作用及机制.方法 临床检测肝硬化PHT患者脾脏动脉内VEGF通路相关蛋白的表达.动物实验观察正常组(N组)7只大鼠和四氯化碳(CCl4)诱导的肝硬化门静脉高压症组(PHT组)7只大鼠的门静脉直径、门静脉血流速度(portal vein blood flow velocity,PBV)、门静脉血流量(portal vein blood flow,PBF)和门静脉压力(portal vein pressure,PP)以及离体肠系膜微动脉对去甲肾上腺素(norepinephrine,NE)的反应性变化.通过SU5416选择性抑制VEGF通路后,对比离体肠系膜微动脉收缩反应性的变化以及肠系膜动脉内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)活化程度的变化.细胞实验中通过原代培养动脉内皮细胞进行体外实验,验证VEGF对eNOS活化的影响.结果 ①肝硬化PHT患者脾动脉VEGF表达明显升高.②动物实验中门静脉直径在N组和PHT组之间差异无统计学意义,PHT组PBV和PBF明显低于N组,SU5416对PHT组PBV及PBF无明显改善作用.③PHT组PP水平明显高于N组,SU5416对PHT组PP无明显降低作用.④PHT组肠系膜微动脉对NE的反应性明显降低,EC50值明显增大,SU5416能部分改善这种低反应性.⑤PHT组肠系膜动脉VEGF、VEGFR-2、eNOS和p-eNOS的蛋白表达较N组明显上调,SU5416能明显降低VEGFR-2与表达和eNOS的活化.⑥体外实验证实,VEGF可促进eNOS的活化.结论 肝硬化PHT内脏动脉中过度生成的VEGF部分通过促进eNOS表达和活化的方式降低内脏动脉对NE的反应性,参与内脏高动力循环的形成.     

从血管再生角度认识门静脉高压症

门静脉高压症是全世界范围的常见病、多发病,病死率较高[1]。由于我国乙型肝炎、血吸虫病发病率较高,故门静脉高压症的发病率明显高于欧美等发达国家,因此在我国对门静脉高压症的预防和治疗更具意义[2]。     

大肠癌组织中TGF-β1和HIF-1α和VEGF的表达及其临床意义

目的:通过检测转化生长因子β1(TGF-β1)、缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)在大肠癌及癌旁组织中的表达情况,探讨其临床意义和预后价值。方法:采用免疫组织化学法检测100例大肠癌及相应的癌旁组织中TGF-β1、HIF-1α和VEGF的表达,分析其表达与大肠癌临床病理特征及预后的关系。结果:1)TGF-β1、HIF-1α和VEGF在大肠癌组织中阳性率分别为63%、59%和63%;在癌旁组织中阳性率分别为11%、22%和13%,三者在大肠癌组织中的表达明显高于癌旁组织(P0.05)。2)TGF-β1的表达与肿瘤的浸润深度明显相关(P0.05);HIF-1α、VEGF的表达与肿瘤的分化程度、浸润深度、淋巴结转移、远处转移及TNM分期明显相关(P0.05)。3)TGF-β1、HIF-1α与VEGF在大肠癌组织中的表达呈正相关(P0.05、P0.01);生存单因素分析显示HIF-1α、VEGF均与患者的预后有关(P均0.05)。结论:大肠癌组织中TGF-β1、HIF-1α、VEGF表达与肿瘤的生物学特征密切相关,可能是肿瘤侵袭转移的机制之一;联合检测TGF-β1、HIF-1α、VEGF对预测肿瘤侵袭转移及判断预后具有一定价值。     

Highly selective portal decompression for bleeding esophageal varices

Since 1974, 112 patients with ruptured esophageal varices, have undergone resection-anastomosis of the supracardial esophagus using the circular suture stapler. Recently, preliminary splenic artery ligature has also been associated, if possible, with systematic ligature of the gastric coronary vein and followed by cardioplasty, to prevent gastro-esophageal reflux and block subcardial venous flow. This highly selective portal decompression (HSPD) procedure provides lasting reduction in blood pressure (confirmed by manometric recordings) in the esophago-cardial region, without any reduction in the distal hepatic flow (no portocaval shunt) or increase in the proximal flow (raised portal pressure). Results were compared with those of the initial, already encouraging, protocol, and demonstrated a tangible improvement after more than one year follow-up. In 50 cases (Child A:16, B:29 and C:5), postoperative mortality was 10% (5 cases) during the first month and 7.5% (3 cases/40) during the first year. There was no specific morbidity due to the additional procedure nor cases of portocaval encephalopathy. During the first postoperative year, the frequency of hemorrhagic complications was one tenth of that during the year before surgery. These very encouraging results suggest the possibility of extending the indications for HSPD in the treatment of recurrent digestive hemorrhages from ruptured esophago-cardial varices, replacing porto-systemic shunts which are sometimes well tolerated but always anti-physiological.     

The mechanism of lysine-vasopressin hemostasis in bleeding esophageal varices.

The effect of vasopressin on the blood flow through experimentally induced esophageal varices and on the musculature of the lower end of the esophagus has been studied. The blood flow was measured by 85Kr injection into the portal vein and selective recording of the radioactivity of the blood flow through the varices. Simultaneous portography and recording of the portal and arterial blood pressure were performed. Following i.v. administration of vasopressin, there was seen a decrease in portal pressure and transient increase in arterial blood pressure. Simultaneously there was observed a decrease in blood flow through the varices, which were no longer visible at portography, while intra-esophageal pressure was increased. It is concluded that there is a dual mechanism of the effect of vasopressin on bleeding from esophageal varices. It reduces the portal pressure and it contracts the esophageal musculature with resultant compression of the afferent radicles to the submucosal esophageal varices.     

The place of Sugiura operation for portal hypertension and bleeding esophageal varices

Fifty patients with portal hypertension and bleeding varices aged 10 months to 72 years were treated with a modified Sugiura, nonshunt operation (n = 26) or shunting procedures (n = 24) in accordance with the following predetermined therapeutic protocol: after resuscitation and diagnostic endoscopy, an emergency mesocaval shunt procedure was carried out if bleeding could not be stopped (group 1, n = 10). When bleeding could be stopped, the patients underwent full investigation and were then treated with either the distal splenorenal (DSR) shunt if the criteria of Warren were satisfied (group 2, n = 14) or with a modified Sugiura procedure in all other circumstances (group 3, n = 26). Patients were evaluated at 1.5 to 6 years. The rates for operative deaths, recurrent hemorrhage, encephalopathy, late deaths, and actuarial patient survival at 6 years were as follows: 20%, 30%, 30%, 20%, and 60% for group 1; 14.3%, 14.3%, 14.3%, 7.2%, and 79% for group 2; and 7.7%, 3.4%, 0%, 0%, and 93% for group 3, respectively. Within 3 months after the Sugiura operation, varices disappeared in 95% of patients and hypersplenism was relieved in all. Major complications were gastric and esophageal leaks in two patients (fatal in one) and temporary dysphagia in six. We conclude that the modified Sugiura nonshunt operation is probably the preferable treatment for variceal hemorrhage in the nonalcoholic patient because it is effective in arresting hemorrhage, has low operative mortality, low recurrence rate, no encephalopathy, and excellent survival rates.     

Short-term portal hemodynamic effects of endoscopic embolization for esophageal varices

BACKGROUND/AIM: Endoscopic embolization (EE) is a specialized treatment that obliterates esophageal varices along with their associated blood supply. The purpose of this study was to investigate the short-term effects of EE for esophageal varices on portal hemodynamics and liver function. METHODS: Thirty patients with esophageal varices were included in this study. The portal blood flow was measured by an ultrasonic duplex Doppler system before and after EE. EE was performed by freehand intravariceal injection of 5% ethanolamine oleate with iopamidol with the aid of a balloon attached to the tip of an endoscope under fluoroscopy. RESULTS: For the blood supply system, endoscopic varicography at the time of EE was able to show the vessels of the cardiac branch of the left gastric vein in 93% of the cases, the cardiac venous plexus in 90%, the trunk of the left gastric vein in 27%, the lesser curvature branch of the left gastric vein in 10%, the fundic branch of the short gastric vein in 13%, and the posterior gastric vein in 13%. For the blood drainage system, endoscopic varicography was able to show the paraesophageal vein in 39% of the cases, the inferior phrenic vein in 17%, and the mediastinal vein in 13%. No clotting was detected after EE in the intra- and extraportal veins in any of the cases. The flow velocities in the main portal vein before and after EE were 14.2+/-3.2 and 15.5+/-3.5 cm/s, respectively, showing no significant change. The cross-sectional area of the portal vein before and after EE was 0.96+/-0.21 and 1.04+/-0.23 cm(2), and the flow volume of the portal vein was 817+/-288 and 930+/-189 ml/min, both also showing no significant change. The blood laboratory parameters showed no significant change after EE. CONCLUSIONS: We conclude that neither portal blood flow nor liver function were damaged by EE, although both the varices and their associated blood supply were obliterated.     

门静脉高压症大鼠胃肠动力变化及其机制的研究

目的　探讨肝硬变门静脉高压症大鼠胃肠动力的改变及其机制。方法　测定肝前、肝内型门静脉高压症大鼠、肝内型门静脉高压症门腔分流大鼠和正常对照鼠的胃肠肌电活动、收缩动力、血浆胃肠激素和肝功能。结果　门静脉高压症大鼠、肝内型门静脉高压症门腔分流大鼠胃肠动力指数 (MI)减小 (P <0 0 5 ) ,消化间期周期性肌电复合波时间延长 (P <0 0 5 ) ,血浆胰高糖素 (Glu)、血管活性肠肽 (VIP)、胃泌素、胃动素水平升高 (P <0 0 5 ) ,血浆白蛋白 (ALB)浓度降低 (P <0 0 5 )。血浆Glu和VIP浓度与空肠MI呈显著负相关 (r =- 0 75 9,r =- 0 6 6 4 ,P <0 0 5 ) ,血浆Glu浓度与空肠周期性肌电复合波时间呈显著正相关 (r =0 80 6 4 ,P <0 0 5 )。结论　Glu和VIP血浆浓度升高是肝硬变门静脉高压症胃肠动力减弱的重要原因。     

The portal circulatory characteristics of patients with esophageal and gastric varices in liver cirrhosis

It was established while examination of 166 patients with hepatic cirrhosis and the portal hypertension syndrome that the varicose esophageal veins are supplied with the blood from left and right gastric veins, and varicose veins of stomach--mainly from short and posterior gastric veins. The regularities of the portal hemodynamics change while the gastric veins varicosity occurrence were revealed: the hepatic portal perfusion lowering and the collateral hepato-fugal blood flow strengthening.     

前列环素与门静脉高压症高动力循环的关系

目的　探讨前列环素 (PGI2 )和一氧化氮 (NO)在门静脉高压症高血流动力循环中的作用。　方法　 66只雄性SD大鼠随机分成 :肝内型门静脉高压症组 (IHPH组 )、肝前型门静脉高压症组 (PHPH组 )和假手术组 (SO组 )。模型制备 1周后再随机分为 3个亚组 ,即对照组、一氧化氮合酶抑制剂L NNA组、消炎痛组。用药 1周后测定股动脉血浆 6 酮 前列腺素F1α(6 keto PGF1α)和NO2 - /NO3- 浓度 ,应用同位素微球技术行血流动力学研究 ,并对NO、PGI2 水平与血流动力学参数行Pearson相关分析。　结果　 (1 )在基础状态下 ,血浆 6 keto PGF1α浓度 ,IHPH鼠 [(1 1 2 3 85± 1 53 64)pg/ml]和PHPH鼠 [(891 88± 83 1 1 )pg/ml]均显著地高于SO鼠 [(72 5 53± 1 0 5 54)pg/ml] ,P <0 0 5 ;血浆NO2 - /NO3- 浓度 ,IHPH鼠 [(73 34± 4 31 ) μmol/L]和PHPH鼠 [(75 2 1± 6 89) μmol/L]均显著高于SO鼠[(58 79± 8 47) μmol/L] ,P <0 0 5。 (2 )与对照组比较 ,L NNA与消炎痛均显著地降低IHPH与PHPH 2组鼠血浆 6 keto PGF1α和NO2 - /NO3- 的浓度 ,P <0 0 5 ;降低IHPH、PHPH 2组鼠的心脏指数 (CI)、门静脉压力 (FPP)和门静脉血流量 (PVI) ,P <0 0 5 ;显著地增高这 2组鼠的平均动脉压 (MAP)、总外周血管阻力 (TPR)和内脏血