血管生成在肝纤维化中的研究进展

血管生成是指在原有的血管结构基础上,内皮细胞以出芽方式,伴随内皮细胞的迁移、扩增、管腔化,形成新的血管的过程。血管生成可分为生理性和病理性两类,病理性血管生成见于以广泛、持续的炎症坏死和纤维化为特征的各种慢性肝脏疾病,包括：慢性乙型肝炎、慢性丙型肝炎、自身免疫性肝炎和原发性胆汁性肝硬化。新血管的形成与不同病因引起的慢性肝病纤维化发展模式紧密相关[1],最终导致肝硬化组织异常血管结构的逐步形成。因此,在现代疾病进展的评价和治疗靶点的研究中,纤维化和血管生成的关系至关重要[2]。血管生成的程度可能会对疾病是否进展到肝硬化产生重要影响,并且是决定纤维化可否逆转的关键因素。     

门静脉高压症性血管病变中局部肿瘤坏死因子-α、血管紧张素原与核因子-kappa B的相关研究

目的 探讨肝硬化门静脉高压症(portal hypertension, PHT)时局部肿瘤坏死因子-α(tumor necrosis-alpha, TNF-α)、血管紧张素原与核因子-kappaB(nuclear factor-kappaB, NF-κB)在门静脉高压症性血管病变中的作用.方法 采用逆转录-聚合酶链反应(RT-PCR)方法检测肝硬化PHT病人脾脏动、静脉组织和正常血管TNF-α mRNA及局部血管紧张素原mRNA的表达情况,用化学发光凝胶电泳迁移率实验(electrophoretic mobility shift assay, EMSA)方法检测局部NF-κB的活性.结果 对照组内脾脏动、静脉组织TNF-α mRNA与局部血管紧张素原mRNA分别为(0.24±0.08)、(0.21±0.12);(0.23±0.09)、(0.18±0.05),显著低于肝硬化PHT组脾动脉、脾静脉组织TNF-α mRNA及局部血管紧张素原mRNA的表达(0.38±0.11)、(0.36±0.16);(0.48±0.12)、(0.43±0.10)(P＝0.025;0.029);对照组脾动、静脉局部NF-κB未被检测到明显的活性,而于肝硬化PHT组检测到显著具有活性的NF-κB表达(P＝0.031),且PHT组脾脏动、静脉TNF-α mRNA表达与NF-κB的活性显著的正相关(r=0.796,P=0.035;r=0.849,P=0.041).结论 肝硬化PHT病人局部TNF-α、血管紧张素原表达增强,NF-κB的活化,三者相互作用,可能是肝硬化门静脉高压症时内脏血管病变形成和发展的原因之一.     

核因子-кappaB的活化在门脉高压性血管病变中的意义

目的 探讨脾脏动、静脉组织核因子-кappaB(nuclear factor-кB,NF-кB)的活化在门静脉高压症(portal hypertension,PHT)性血管病变中的作用及意义.方法 采用化学发光凝胶电泳迁移率实验(chemiluminescent electrophoretic mobility shift assay,EMSA)方法检测肝硬化PHT患者脾脏动、静脉和正常血管NF-кB的活性.结果 对照组脾动、静脉NF-кB未被检测到明显的活性,其相对表达值分别为(0.19±0.12)和(0.25±0.16);而于肝硬化PHT组脾动、静脉内检测到显著具有活性的NF-кB表达(1.44±0.23)和(1.38±0.18),P＜0.05.结论 肝硬化PHT血管组织NF-кB的活化可能是肝硬化P-HT时内脏血管病变形成和发展的始动原因之一.     

核因子-κappaB的活化在门脉高压性血管病变中的意义

目的探讨脾脏动、静脉组织核因子-κappaB（nuclear factor—κB，NF—κB）的活化在门静脉高压症（portal hypertension，PHT）性血管病变中的作用及意义。方法采用化学发光凝胶电泳迁移率实验（chemiluminescent electrophoretic mobility shift assay，EMSA）方法检测肝硬化PHT患者脾脏动、静脉和正常血管NF—κB的活性。结果对照组脾动、静脉NF—κB未被检测到明显的活性，其相对表达值分别为（0．19±0．12）和（0.25±0.16）；而于肝硬化PHT组脾动、静脉内检测到显著具有活性的NF—±B表达（1.44±0．23）和（1．38±0．18），P〈0．05。结论肝硬化PHT血管组织NF—κB的活化可能是肝硬化PHT时内脏血管病变形成和发展的始动原因之一。     

血管新生及其调节

1　血管新生概念新血管的形成在很多生理过程中是必要的 ,如胚胎发生、女性生殖、疮口愈合以及缺血组织的新血管形成等。在了解血管生长调节机制的基础上 ,对很多缺血性疾病提供了新的治疗选择。血管形成 (ｖａｓｃｕｌｏｇｅｎｅｓｉｓ)和血管新生 (ａｎｇｉｏｇｅｎｅｓｉｓ)是新血管形成的主要机制。血管新生指的是从已经存在的血管上生长出毛细血管。病理性的血管新生包括关节炎、糖尿病视网膜病变、肿瘤的生长和转移等的新血管形成。血管新生疗法指的是用内生的或使用外源性的生长因子等方法促进新血管生成 ,包括缺血组织中的侧支循环…     

局部Ang Ⅱ水平与ERK的活化在人门静脉高压症脾静脉血管病变中的作用

目的探讨血管紧张素Ⅱ（AngⅡ）水平与细胞外信号调节激酶（ERK）活化在人门静脉高压症（PHT）脾静脉血管病变中的作用及可能机制。方法选取乙型肝炎感染后肝硬化PHT患者26例为PHT组;选取因外伤性脾破裂行脾切除术患者10例为对照组。放射免疫分析法（RIA）检测脾静脉中AngⅡ水平;免疫组织化学法和蛋白免疫印迹法检测脾静脉中ERK的表达。结果PHT组脾静脉组织AngⅡ水平（248.91±48.31）ng/L,显著高于对照组（143.35±36.45）ng/L（P〈0.01）。蛋白免疫印迹/免疫组织化学染色均显示PHT组脾静脉ERK表达较对照组明显增加。结论PHT时脾静脉组织AngⅡ水平升高,ERK表达增加。局部AngⅡ升高及ERK信号传导通路的激活可能与门静脉高压症的形成和维持有关。     

肿瘤的抗血管生成治疗:现状与问题

正常组织血管生成是血管生成抑制因子和促进因子间的复杂平衡,而在肿瘤中,该平衡向促进因子一端的偏移,导致病理性血管生成及肿瘤血管的不规则生长。     

门静脉高压症动脉血管低反应分子机制研究进展

全身和内脏的高血流动力循环 (心输出量增加 ,内脏充血 ,外周血管阻力下降 )在维持和加重门静脉高压症 (portalhypertension ,PHT)中起极为重要的作用[1] 。而动脉血管对内源性收缩物质如去甲肾上腺素、血管加压素、血管紧张素 -Ⅱ、内皮素 -Ⅰ等低反应导致的内脏小动脉扩张是PHT高血流动力循环的重要发病因素[2 ] ,虽然动脉低反应推测与受体下调和 /或脱敏及过量生成的内源性舒血管物质有关 ,但门静脉高压症时动脉血管平滑肌低反应的分子机制还不十分清楚。现就门静脉高压症时动脉血管平滑肌低反应的分子机制从内源性血管活性物质受体水…     

肿瘤血管生成的调节机制研究进展

肿瘤血管生成 (angiogenesis)是指肿瘤细胞诱导的微血管生长以及肿瘤中血液循环建立的过程。随着对肿瘤发生机制研究的不断深入 ,肿瘤血管生成在肿瘤发展中的重要地位及抗血管生成治疗肿瘤的作用成为研究的热点。本文就近年来对肿瘤血管生成的调节机制研究进展综述如下。1　肿瘤血管生成过程及特点　　机体的血管形成包括血管发生和血管生成两个过程 ,即胚胎发育形成原始血管结构及以出芽方式继续增生分化出新生血管的过程。生理条件下此过程是严格受控的。而病理的血管生成 ,特别是肿瘤条件下的血管生成则呈一持续、无控性的过程。肿瘤血管…     

RhoA/Rho激酶信号途径在门静脉高压发病机制中的研究进展

门静脉高压(PHT)是肝硬化后期的一个重要并发症,其引起的上消化道出血、脾大、腹腔积液、侧支循环形成严重影响患者的生存质量。由于PHT发病机制复杂、肝内和肝外存在诸多矛盾,导致临床上缺乏有效治疗PHT的药物,这也是目前PHT治疗的瓶颈问题之一。因此,深入研究PHT的形成机制,开发安全有效、不良反应少的药物一直是该领域的研究热点。调节血管收缩的Rho A/Rho激酶信号途径异常可能是PHT形成的关键机制之一。该文总结了近年来Rho A/Rho激酶信号途径在PHT发病机制中的研究进展,旨在为开发治疗PHT的药物提供新思路。     

Angiogenesis and Hepatic Fibrosis: Western and Chinese Medicine Therapies on the Road

Hepatic fibrosis is a common feature of almost all chronic liver diseases. Formation of new vessels (angiogenesis) is a process strictly related to the progressive fibrogenesis which leads to cirrhosis and liver cancer. This review mainly concerns the relationship between angiogenesis and hepatic fibrosis, by considering the mechanism of angiogenesis, cells in angiogenesis, anti-angiogenic and Chinese medicine therapies.     

Inhibition of Pathological Angiogenesis of Chinese Medicine against Liver Fibrosis

Pathological angiogenesis of liver which includes liver sinusoidal capillarization due to lose of fenestraes of liver sinusoidal endothelial cells (LSECs) and formation of new vascular, is a crucial mechanism responsible for origination and development of liver fifibrosis and closely involves in the development of cirrhosis and hepatic cancer. Anti-neovascularization medicine such as sorafenib can decrease portosystemic shunts, improve splanchnic hyperdynamic circulation, lower portal hypertension, while it can not be applied in clinic due to its serious toxic and side reactions. Chinese herbal formula can effectively inhibit pathological angiogenesis of liver, improve microcirculation of liver, and decrease the probability of gastrointestinal hemorrhage in cirrhotic patients. Different Chinese herbal formula are of different characteristics on inhibiting pathological angiogenesis in liver fifibrosis, which partly explains synergistic effect of different compatibility of Chinese materia medica and opens up good vista for Chinese medicine against liver fifibrosis through inhibiting angiogenesis.     

Management of choledochal cyst with portal hypertension

Portal hypertension (PHT) is a rare complication associated with choledochal cysts. Management issues of PHT patients are inadequately addressed, as its incidence is low and underlying causes variable. We report three cases of choledochal cyst with PHT. All patients had type IVa choledochal cysts, and the causes of PHT were secondary biliary cirrhosis (SBC) (two cases) and alcoholic liver disease (one case). Clinical presentation included jaundice, gastrointestinal bleeding and ascites. One patient with SBC successfully underwent excision with Rouxen-Y hepaticojejunostomy, while the patient with cholangitis was managed with endoscopic retrograde cholangiopancreatography stenting. The last patient with alcoholic liver disease was managed conservatively for seven years and died of liver failure. Management of choledochal cysts depends on the severity of liver disease in cases of cirrhosis of unrelated cause, while those with SBC should be considered for surgical management. Endoscopic stenting may be considered as a temporary measure in high-risk cases.     

Microcirculation of Liver Cancer, Microenvironment of Liver Regeneration, and the Strategy of Chinese Medicine

Microcirculation of liver cancer is the micro-vascular system which comes from the tissue of liver cancer. It can offer the nutritional requirement for accelerating the cancer cell proliferation and metastasis. The intrinsic mechanism of angiogenesis is the key link in the formation of liver cancer microcirculation system. Liver regeneration microenvironment also plays an important role in the construction of liver cancer microcirculation, through the improvement of liver regeneration microenvironment affecting tumor microcirculation is the new strategy of prevention and treatment of liver cancer. In recent years, it is found that many kinds of Chinese medicine can inhibit angiogenesis, decrease the microvessel density, and delay or prevent the development of liver cancer.     

Surgical therapy for portal hypertension in patients with cirrhosis in China: present situation and prospects

Surgical therapy for portal hypertension (PHT) in patients with cirrhosis has long been controversial,and various operative approaches have been used to prevent or manage such lethal complications as gastroesophageal variceal hemorrhage. However, over a century various portazygos devascularization and shunt approaches have been developed or modified, but the therapeutic effects have not been satisfactory till 1963 when Starzl did the first liver transplantation in the world, which provides a new hope to the surgical treatment of PHT.     

Surgical therapy for portal hypertension in patients with cirrhosis in China: present situation and prospects

Surgical therapy for portal hypertension (PHT) in patients with cirrhosis has long been controversial,and various operative approaches have been used to prevent or manage such lethal complications as gastroesophageal variceal hemorrhage. However, over a century various portazygos devascularization and shunt approaches have been developed or modified, but the therapeutic effects have not been satisfactory till 1963 when Starzl did the first liver transplantation in the world, which provides a new hope to the surgical treatment of PHT.     

Surgical therapy for portal hypertension in patients with cirrhosis in China: present situation and prospects

Surgical therapy for portal hypertension (PHT) in patients with cirrhosis has long been controversial,and various operative approaches have been used to prevent or manage such lethal complications as gastroesophageal variceal hemorrhage. However, over a century various portazygos devascularization and shunt approaches have been developed or modified, but the therapeutic effects have not been satisfactory till 1963 when Starzl did the first liver transplantation in the world, which provides a new hope to the surgical treatment of PHT.     

Surgical therapy for portal hypertension in patients with cirrhosis in China: present situation and prospects

Surgical therapy for portal hypertension (PHT) in patients with cirrhosis has long been controversial,and various operative approaches have been used to prevent or manage such lethal complications as gastroesophageal variceal hemorrhage. However, over a century various portazygos devascularization and shunt approaches have been developed or modified, but the therapeutic effects have not been satisfactory till 1963 when Starzl did the first liver transplantation in the world, which provides a new hope to the surgical treatment of PHT.     

Surgical therapy for portal hypertension in patients with cirrhosis in China: present situation and prospects

Surgical therapy for portal hypertension (PHT) in patients with cirrhosis has long been controversial,and various operative approaches have been used to prevent or manage such lethal complications as gastroesophageal variceal hemorrhage. However, over a century various portazygos devascularization and shunt approaches have been developed or modified, but the therapeutic effects have not been satisfactory till 1963 when Starzl did the first liver transplantation in the world, which provides a new hope to the surgical treatment of PHT.