大鼠肝内型门脉高压症形成中门静脉力学性质的变化

目的观察大鼠肝内型门脉高压症形成中门静脉零应力状态及轴向拉伸时张应力．伸长比关系的动态变化，探讨门静脉生物力学特性的变化在门脉高压症形成中的作用。方法以60％四氯化碳(CCl4)皮下注射法制备肝内型门脉高压症大鼠模型，采用生物力学技术测定CCl4注射第2、4、6、8、10周大鼠门静脉零应力状态张开角和轴向拉伸时张应力，伸长比关系，并同步监测大鼠门静脉压力(PVP)、门静脉流量(PVF)、平均动脉压(MAP)、门静脉阻力(PVR)和内脏血管阻力(SVR)等血液动力学指标的动态变化。结果随着CCl4注射时间的延长，实验组大鼠的血液动力学指标发生了显著的变化。与之相对应．大鼠门静脉张开角及轴向拉伸参数b亦逐渐增大，从注射第10周起与对照组相比具有统计学差异(P＜0．05)。结论门脉高压症大鼠存在高动力循环状态(HCS)。HCS可引起门静脉血管生物力学特性的变化。     

胆石症合并肝硬化门脉高压的临床特点及治疗分析

<正>门脉高压由门静脉系统压力升高所致,按照病因可分为肝前型、肝内型和肝后型,其主要致病因素为血吸虫病和肝硬化[1]。由于肝硬化门脉高压患者的肝功能损害、凝血机制异常和低蛋白血症等临床表现,其合并胆石症发病率较高,是正常人发病率的2~3倍[2]。且胆石症合并肝硬化门脉高压使患者术中出血风险增加、术后并发症发生率高,给治疗带来了较大挑战。为分析胆石症合并肝硬化门脉高压的临床特点以及术中、术后情况,笔者选取我院2007年4月至2010年5月收治的17例胆石症合并肝硬化门脉高压患者进行了分析,现将研究过     

肝硬变门脉高压症大鼠舌脉的血流动力学变化及其发生机制的研究

用小剂量ＣＣＩ＿４皮下注射与脂肪饲料及乙醇喂饲复制肝硬变门脉高压性瘀证大鼠模型，以探索中医舌脉变化与舌深静脉压、门脉压、门脉血流量之间的关系。实验结果表明，实验组大鼠均已形成肝硬变，并以假小叶形成的三期病变为主，肝窦不清晰，间隙变窄乃至闭塞；舌腹面粘膜下乃至肌间、食管及胃肠粘膜下均有微小血管淤血，脾脏淤血更为明显；舌深静脉压力升高，与门脉压升高呈正相关；门脉血流量明显减少，与正常对照组大鼠比较Ｐ＜０．０１．认为肝硬变门脉高压性瘀症的舌脉粗张与细络瘀血主要是因门脉血经门一腔侧支循环回流入上腔静脉，引起上腔静脉阻力增大，压力增高，导致舌的静脉系统回流受阻，使舌深静脉血流量增多，压力升高所致。     

门脉高压大鼠肺微血管周细胞α-SM-actin表达的改变

目的:通过对胆汁性肝硬化门脉高压大鼠肺微血管周细胞α-SM-ac-tin表达的测定,探讨门脉高压肺部微血管是否受累,以及周细胞在其中的作用。方法:实验分为三组:模型组、对照组及治疗组(银杏注射液治疗)。应用结扎胆总管复制胆汁性肝硬化门脉高压模型,采用Masson法、免疫组织化学染色、图像分析等技术研究肝硬化门脉高压对大鼠肺微血管周细胞α-SM-actin表达的影响。结果:模型组平均吸光度0.3499±0.089,对照组平均吸光度0.3344±0.0890,治疗组平均吸光度0.2890±0.102,对三组结果进行两两非配对t检验,均具显著性差异(P0.01)。结论:肝硬化门脉高压可刺激肺微血管周细胞增殖或向平滑肌细胞转化,而银杏注射液能抑制这种改变。这表明门脉高压肺部微血管同样受累,周细胞在病变中可能具有重要的意义。     

门脉高压性肠病组织病理学观察北大核心CSCD

1991年Kozarek等[1]首次提出门脉高压性肠病的概念.指继发于肝门静脉高压以肠道血管扩张为特征的一种病变.包括门脉高压性小肠病和门脉高压性结肠病。门脉高压性肠病的临床和内镜表现已有不少报道,但对病理组织学表现的报道不多[2-3]。我们对存在肝硬化门脉高压的10例结肠活检标本和2例小肠切除标本进行了组织病理学观察。     

门脉高压症脾静脉壁的病理改变及组化研究

目的:为了解门脉高压症患者脾静脉壁的病理改变。方法:对15例门脉高压症患者切除脾叶静脉壁进行了普通染色(H.E)和免疫组织化学染色,并以外伤脾为对照,观察其病理改变。结果:15例门脉高压症脾静脉壁均有不同程度的平滑肌肥大、纤维组织增生,13例脾叶静脉壁内皮细胞、脾窦IgG、IgA、C_3、C_4阳性,阳性串为86.7％;10例外伤脾中仅1例阳性,阳性率为10.0％,且无明显的平滑肌肥大和纤维组织增生的改变。结论:门脉高压症患者门静脉系统本身的病理改变以及免疫病理损伤可能影响门脉高压的发生和发展。     

3D DCE MRP在评价肝硬化门脉高压症门静脉系统血管解剖及侧支循环的价值

目的:探讨三维动态对比增强磁共振门脉血管造影(3DDCEMRP)在肝硬化门脉高压症门静脉系统及门体侧支循环显像中的应用价值.方法:对19例肝硬化门脉高压症组病人及51例非肝硬化对照组行3DDCEMRP检查,测量门脉系统各主要干支的径线并比较两者差异;于3DDCEMRP检查前后10d内,对所有肝硬化症组患者行门脉间接造影,以其结果为标准,分析侧支循环发生的部位和分布范围,评价两者的符合情况.结果:肝硬化门脉高压症组MPV、SPV及SMV直径明显大于对照组(P<0.05),门脉分支级数明显减少;但Child A、B级患者间MPV直径及门脉分支级数的减少无明显差别(P>0.05).同时,3D DCE MRP显示2例门脉主干海绵样变并检出48条肝外侧支血管,与DSA结果相对照,除1例脐静脉开放及1例自发性脾肾分流未见显示外,其余侧支循环在3D DCE MRP 上均清楚显影,总符合率为96.0%(48/50).结论:3DDCEMRP能较好显示门脉系统的解剖影像,并对曲张静脉、侧支循环显影良好,也是诊断门脉海绵样变的有效方法.对于门脉高压症的诊断及手术治疗有重要指导意义.     

门静脉高压症猪肝动脉的生物力学特性

目的：建立猪门静脉高压症模型,探讨门静脉高压症对肝动脉的生物力学特性的影响。方法：猪以四氯化碳、苯巴比妥、乙醇,配合高脂、低蛋白、低胆碱饮食进行混合饲养。通过脾静脉插管测压,取肝动脉在生物软组织力学试验机上测定其压力-直径关系,计算机图像分析测量肝动脉两端血管环的张开角及其几何形态学指标。结果：实验组门静脉压(4．17±1．03)kPa明显大于对照组(1．51±0．79)kPa,肝动脉的各向同性增量弹性模量、血管容积弹性模量和血管压力-应变模量均随压力的上升而增大,在相同压力下明显大于对照组。肝动脉的顺应性显著低于对照组,而张开角显著增加。结论：门静脉高压症时,肝动脉的生物力学特性发生了显著变化。     

肝前性门脉高压大鼠胰岛功能的变化

目的：探讨肝前性门脉高压大鼠胰岛α、β细胞功能及其与循环血液中胰岛素及胰高血糖素水平变化的关系。方法：采用部分结扎门静脉的方法复制肝前性门脉高压,假手术及正常鼠的胰岛进行分离和纯化,并对其体外生物学活性进行检测。结果：肝前性门脉高压组大鼠循环血液中胰岛素及腹高血糖素水平明显高于正常组大鼠（P＜0．01）。肝前性门脉高压级大鼠分离纯化的胰岛经体外培养48h或在含糖基质中孵育2h后释放胰岛素量明显低于正常,而陵高血糖素明显高于正常（P＜0．01）。结论：胰岛α细胞分泌功能增加可能有助于解释高胰高血糖素血症的发生;门脉高压时,循环血液中胰岛素水平增加,但哪胞功能低于正常。     

门脉高压症患者胃粘膜微循环障碍与血清中TNF、ET浓度变化的相关性

目的：研究门脉高压性胃粘膜病变（ＰＨＧ）的实质及其与血清中ＴＮＦ、ＥＴ的浓度变化的关系。方法：对３０例门脉高压性胃粘膜病变患者和１５例门脉高压症非胃粘膜病变（ＮＰＨＧ）患者的胃粘膜进行光镜、透射电镜观察,同时应用放免法检测二组血清中ＴＮＦ、ＥＴ的浓度。结果：门脉高压时胃粘膜微循环障碍是ＰＨＧ形成的实质;门脉高压病患者血清中ＴＮＦ、ＥＴ的浓度变化与ＰＨＧ的发生、发展呈正相关;比较二组血清中ＴＮＦ、ＥＴ浓度差异有显著性（Ｐ＜０．０１）。结论：门脉高压时胃粘膜微循环变化包括有细胞机制和免疫反应二个方面的参与。     

血吸虫病性门静脉高压症兔肝脏微血管构筑变化的研究

目的:探讨血吸虫病门静脉高压症时肝脏微血管构筑的变化及其可能在全身高动力循环状态中的作用。方法:采用腹部敷贴法感染血吸虫尾蚴建立血吸虫病性肝纤维化模型,经插管检测心输出量(CO)、平均动脉压(MAP)、心率(HR)和肝静脉嵌塞压(WHVP),按公式计算心脏指数(CI)、外周血管阻力(SVR);通过血管铸型方法观察肝脏微血管构筑。结果:与正常兔比较,血吸虫病兔CO、CI明显增高,MAP和SVR显著降低,WHVP升高,两组间HR差异无统计学意义。肝脏微血管铸型观察,血吸虫病时肝内微血管形态和比例严重失常,肝窦显著膨大,门静脉主干增粗,肝内形成广泛的小吻合支,其间以门静脉终末支与肝静脉终末支、门静脉小分支直接引流入肝静脉多见。结论:血吸虫病性门静脉高压症兔存在肝内门-体分流病理改变,可能是形成全身高动力循环状态并维持门静脉高压的一个重要环节。     

Contractility,Muscle Mass and Agonist Sensitivity of Isolated Portal Veins from Normo- and Hypertensive Rats

Properties of the longitudinal smooth muscle of portal veins from normotensive Wistar rats, adult (NCR) and young (NCR_y); spontaneously hypertensive Okamoto rats, adult (SHR) and young (SHR_y); and adult Wistar rats with renal hypertension (RHR) were studied in vitro and histologically. Some aortic strips from SHR and SHR_y were compared with controls. In response to noradrenaline (NA) and acetylcholine (ACh) greater maximum force was developed by veins from all hypertensive groups than by those from control rats. Cross-sectional area of the longitudinal muscle of veins from SHR but not SHR nor RHR was greater than control. Maximum stress in response to agonists was greater in both SHR and RHR than NCR. ED_so-values for NA and ACh were lower in portal veins from SHR than NCR but not from RHR nor SHR_y compared to controls. Denervation did not abolish any of the differences between SHR and NCR. Aortic strips from SHR developed less maximum force to NA and ED₅₀ was greater than those from NCR. i.e. opposite to the findings in portal veins. Low levels of external Ca^2- reveal altered calcium handling in veins from SHR compared to controls. It is concluded that portal veins from hypertensive rats are functionally different from those of normotensive rats and differ in SHR compared to RHR. It is suggested that the altered functional properties of portal vein, but not of aorta, in several respects resemble those of arterial resistance vessels. The implications of these findings are discussed in terms of mechanisms of hypertension in these animal models.     

门静脉高压症患者血浆内源性硫化氢含量的变化和意义

目的:观察血浆内源性硫化氢(H2S)在门静脉高压症不同Child级别患者中的差异及其在门静脉高压症发病中的可能作用。方法:测定2007年9月～2007年12月在我院住院治疗的门静脉高压症患者(23例)和同期体检健康人群(25例)的血浆H2S水平、肝功能、门静脉管径,分析血浆H2S含量差异与门静脉高压症的关系。结果:门静脉高压症患者血浆H2S水平较健康人低;Child不同级别H2S含量存在明显差异,血浆H2S含量与门静脉管径具有负线性相关关系。结论:内源性H2S可能参与门静脉高压症的病理过程。     

门静脉内皮细胞损伤与门静脉高压症相互关系的研究

采用Masson三色染色法,辅以形态学观察,研究肝硬变病人(n=30)肝内外门静脉的内皮细胞变化。发现血管内皮细胞有明显损伤,伴血栓形成及管壁结构改建。提示血管内皮细胞损伤与门静脉高压症有密切关系。     

Relationship between Tetrahydrobiopterin and Portal Hypertension in Patients with Chronic Liver Disease

Tetrahydrobiopterin (BH4) is an essential cofactor in NO synthesis by endothelial nitric oxide synthase (eNOS) enzymes. It has been previously suggested that reduced intrahepatic BH4 results in a decrease in intrahepatic NO and contributes to increased hepatic vascular resistance and portal pressure in animal models of cirrhosis. The main aim of the present study was to evaluate the relationship between BH4 and portal hypertension (PHT). One hundred ninety-three consecutive patients with chronic liver disease were included in the study. Liver biopsy, measurement of BH4 and hepatic venous pressure gradient (HVPG) were performed. Hepatic fibrosis was classified using the Laennec fibrosis scoring system. BH4 levels were determined in homogenized liver tissues of patients using a high performance liquid chromatography (HPLC) system. Statistical analysis was performed to evaluate the relationship between BH4 and HVPG, grade of hepatic fibrosis, clinical stage of cirrhosis, Child-Pugh class. A positive relationship between HVPG and hepatic fibrosis grade, clinical stage of cirrhosis and Child-Pugh class was observed. However, the BH4 level showed no significant correlation with HVPG or clinical features of cirrhosis. BH4 concentration in liver tissue has little relation to the severity of portal hypertension in patients with chronic liver disease.

Graphical Abstract

相似文献   

肝硬化门静脉高压患者免疫功能及血清细胞因子水平变化分析

目的探究肝硬化门静脉高压患者免疫功能及血清C反应蛋白(CRP)、降钙素原(PCT)、前列腺素E(PGE)等因子变化情况。方法选择2014年2月至2019年3月我院收治的81例肝硬化门静脉高压患者及50例健康志愿者作为研究对象,分别纳入门静脉高压组及对照组。测定天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、白蛋白(ALB)、总胆红素(TBIL)、门静脉内径(Pvd)指标;测定CD3^+、CD4^+、CD8^+T淋巴细胞比例、CD4^+/CD8^+水平及血清CRP、PCT、PGE等细胞因子水平。结果①门静脉高压组ALT、AST、TBIL、Dpv等指标显著高于对照组(P<0.05),ALB显著低于对照组(P<0.05)。②门静脉高压组患者CD3^+、CD4^+T淋巴细胞亚群计数及CD4^+/CD8^+显著低于对照组(P<0.05),CRP、PCT、PGE等细胞因子指标高于对照组(P<0.05)。③随肝功能分级的升高,患者CD3^+、CD4^+T淋巴细胞亚群比例及CD4^+/CD8^+降低,血清CRP、PCT、PGE水平升高,差异具有统计学意义(P<0.05)。④Spearman相关性分析示,肝功能分级与CD4^+、CD4^+/CD8^+等免疫指标呈负相关(P<0.05),与CRP、PCT、PGE水平呈正相关(P<0.05);Pearson相关性分析示,Dpv与CD4^+/CD8^+呈负相关,与PCT、PGE水平呈正相关(P<0.05)。结论肝硬化门静脉高压患者可出现免疫功能失调及细胞因子紊乱,这一变化与肝功能及门静脉压力相关,临床可将其作为评估患者病情的参考指标。     

A Case Report of Early Idiopathic Portal Hypertension

We report herein a case (46 years, female) of very early idiopathic portal hypertension. During an examination for in situ uterine cervical cancer, splenomegaly and hypersplenism were incidentally found. CT and MRI showed a nonatrophic liver with dilated portal veins and marked splenomegaly. The portal venous blood flow was increased, while portal venous blood pressure was not high. The spleen (1,220 g) showed hyperplasia of white pulp and congestion. The lobular architecture of the liver was well-preserved, and the subcapsular regions were not atrophic or dropped out. The portal tracts were not fibrotic, and portal veins were neither stenotic nor sclerotic. Instead, lymphoid cell infiltrations were found in about half the portal tracts, and there was subendothelial mononuclear cell infiltration of small portal vein branches. The hepatic lobules showed non-specific reactive change. This case suggests that early hepatic changes recognizable histologically in this disease are lymphoid cell infiltration of the portal tract and of subendothelial regions of portal vein branches, and nonspecific lobular hepatitis. These hepatic changes, as well as marked splenomegaly, may represent an altered immunophenomenon of this disease.     

Pathogenesis of portal sclerosis in the liver with idiopathic portal hypertension. Observations of 19 autopsy cases and animal experiments

The pathomorphological changes of intrahepatic portal veins were studied in 19 autopsy cases of idiopathic portal hypertension (IPH), and the pathogenesis of portal sclerosis was discussed by the observations on the human and experimental materials. The degree and morphological appearance of intimal lesions vary from vessel to vessel. Fibro-cellular proliferation of subendothelial tissue and incorporation of organized mural thrombi were suggested as the cause of intimal thickening in the portal veins. Animal experiment showed that injury of portal vein wall was followed by intimal hyperplasia and/or incorporation of mural thrombi, and resulted in portal sclerosis similar to that of IPH liver. The cause of portal phlebosclerosis in IPH can not be explained by passive congestion alone. There might be a certain possibility of direct injurious effect in the vessel wall in the pathogenesis of portal lesions of IPH. The following pathogenesis of portal sclerosis in IPH is postulated: phlebo-sclerotic changes of the portal veins are initiated by injury to the vessel wall due to unknown cause(s) and accelerated by secondary thrombosis and/or mechanical injury due to increased portal pressure.     

肝静脉与门静脉的解剖及其在经颈静脉肝内门体分流术中的应用

目的：探讨肝静脉与门静脉的解剖及在经颈静脉肝内门体分流术（TIPS）中的应用。方法：在PUBMED、CNKI及维普等数据库中,查阅近年来国内外有关肝静脉、门静脉的正常解剖与变异及其在TIPS中应用的文献,进行分析总结。结果：肝静脉系统主要由肝右静脉、肝中静脉、肝左静脉3支组成,肝左静脉发生变异最多,肝中、右静脉变异相对少见。门静脉在肝门处进入肝脏,以分为左支和右支两主干这一类型居多,其解剖形态因地区、种族等因素而有差异。肝静脉和门静脉呈向后向上与向前向下的空间关系,经典TIPS是从肝右静脉距下腔静脉入口约2cm处向门静脉分叉部或右支内穿刺建立分流道。结论：肝静脉、门静脉的正常解剖与变异及其空间关系对顺利完成TIPS的操作至关重要。熟悉肝静脉、门静脉正常解剖和变异可提高TIPS的成功率,减少和避免并发症的发生。