垂体后叶素和特利加压素降低门胆汁性肝硬化大鼠静脉高压对肝组织氧分压的影响

目的:探讨垂体后叶素和特利加压素降低肝硬化门脉高压时对肝组织氧分压的不同影响。方法:采用胆总管结扎法制作胆汁性肝硬化模型,40只大鼠随机分成2组:垂体后叶素组(n_1=20),特利加压素组(n_2=20),两组分别从门静脉缓慢注入垂体后叶素和特利加压素,连续观察用药前及用药后5,10,15,20,25,30min的门静脉压及肝组织氧分压。结果:两组用药后门静脉压均明显降低,两组间无显著差异(t=0.39 P>0.05);垂体后叶素组用药后肝组织氧分压明显下降,特利加压素组无明显下降,两组间有显著差异(t=9.19P<0.01)。结论:垂体后叶素降低门静脉压时肝组织氧分压明显下降,而特利加压素在降低门静脉压时肝组织氧分压无明显降低,是治疗急性食管、胃静脉曲张破裂出血较理想的药物。     

特利加压素、垂体后叶素对正常及门脉高压兔门脉血流动力学影响的研究

目的　通过比较特利加压素 (terlipressin或glypressin)和垂体后叶素 (pituitrin)对正常及门脉高压兔血流动力学的影响 ,探讨特利加压素治疗门脉高压症的意义。方法　新西兰大白兔 2 0只 ,分为 4组 :①正常兔 +特利加压素组 (4只 ) ;②正常兔 +垂体后叶素组 (4只 ) ;③门脉高压兔 +特利加压素组 (7只 ) ;④门脉高压兔 +垂体后叶素组 (5只 )。部分结扎门静脉主干制备肝前性门脉高压兔模型。在静脉注射特利加压素、垂体后叶素前及注射后 1、5、10、15、2 0、30、6 0min ,观察对门静脉压力 (PVP)、门静脉血流量 (PVF)、心率 (HR)及平均动脉压 (MAP)波动幅度影响。结果　两药的最大降压作用相比 ,差异无显著性 (P >0 .0 5 )。但注射药物后 6 0min ,垂体后叶素的作用基本消失 ,而特利加压素仍有明显的降压作用 (P <0 .0 5 )。而且 ,特利加压素所致门脉高压兔HR、MAP的最大振幅仅为 (6 .5± 0 .5 ) %和(9 .6± 0 .7) % ,低于垂体后叶素的 (2 3.3± 2 .3) %和 (15 .7± 0 .7) % (P <0 .0 5 )。结论　应用特利加压素治疗门脉高压比垂体后叶素更为安全而持久有效     

特利加压素治疗门静脉高压症相关并发症的研究进展

门静脉高压症是多种原因导致的门静脉与下腔静脉间的压力梯度出现病理性增加,内脏循环与体循环系统血流动力学发生改变,进而导致一系列并发症。病因多与肝内血管阻力增加及门静脉血流改变有关,其中肝硬化是最常见的病因。一般慢性肝炎终末期都会有肝硬化的表现,临床特征起初显示为高动力循环状态,即心输出量增加,外周血管阻力降低。随着病情的进展,门静脉压力升高,肝功能减退,高动力循环不能代偿,导致相     

氯沙坦对肝硬化门静脉高压症大鼠肝静脉压力梯度的影响

目的:探讨氯沙坦对肝静脉压力梯度(HVPG)的作用及其机制.方法:采用复合因素法制作大鼠肝硬化门静脉高压症(PHT)模型,49只雄性Wistar大鼠随机分为5组:正常对照组、模型对照组、3个治疗组(分别给予10mg·kg-1·d-1、 5mg·kg-1·d-1、2.5mg·kg-1·d-1 3种剂量氯沙坦).治疗21天结束后,进行各项指标检测.结果:①与正常对照组比较,模型对照组肝静脉楔入压(WHVP)、HVPG显著升高(P＜0.05),游离肝静脉压(FHVP)、平均动脉压(MAP)和心率(HR)无明显变化;内皮型-氧化氮合酶(eNOS)的表达减少,肝匀浆氧化氮(NO)水平无明显变化但内皮素(ET)水平升高(P＜0.05);②治疗21天结束后,与模型对照组比较,各治疗组HVPG均有显著下降(P＜0.05),3组之间比较差别无统计学意义.而高剂量组导致了MAP的显著下降(P＜0.05);③与模型对照组比较,各治疗组eNOS的表达显著升高(P＜0.05),肝内NO含量增加而ET水平降低(P＜0.05),各治疗组之间比较差别无统计学意义.结论:氯沙坦能有效地降低肝硬化大鼠的HVPG,中、低剂量具有与高剂量类似的治疗效果,且对全身血流动力学影响小.     

缬沙坦降低大鼠肝硬化门静脉高压的实验研究

如何预防肝硬化门静脉高压（PHT）所致的食管静脉曲张破裂出血（EVB）是临床面临的一个重要课题.药物治疗肝硬化PHT预防EVB是目前研究的热点.普萘洛尔临床研究报道较多,但其不良反应限制其临床应用,联合用药是目前研究的一种趋势.近年有研究报道,血管紧张素Ⅱ（AngⅡ）1型受体拮抗剂有降低门脉压力的作用,但不引起全身血流动力学变化.本实验观察缬沙坦降低大鼠肝硬化PHT的疗效并探讨其作用机制.     

肝积合剂对肝硬化门静脉高压的影响

目的：探讨肝积合剂对肝硬化门脉高压的影响。方法：将60例肝硬化门脉高压症患者随机分为两组，治疗组患者口服中药肝积合剂，对照组患者口服心得安，共3个月。用彩色双功能多普勒超声诊断仪测量门静脉内径、脾静脉内径、门静脉血流速度、脾静脉血流速度。采用胃镜观察食管静脉曲张部位、条数、形态、颜色及胃底有无静脉曲张。结果：肝积合剂可显著缩小肝硬化患者门静脉及脾静脉内径、加快血流速度、减少血流量。尤其在加快门静脉、脾静脉血流速度及减少血流量上与心得安比较，差异有显著性意义（P〈0．05）。结论：肝积合剂对肝硬化门脉高压症有一定的防治作用。     

丹参酚酸B盐对肝硬化大鼠门静脉高压及肝组织中内皮素-1的影响

[目的]观察丹参酚酸B盐(SA-B)对肝硬化门静脉高压的疗效。[方法]以0.5%二甲基亚硝胺(DMN)腹腔注射建立大鼠肝硬化动物模型,模型成功后开始给予SA-B治疗,测定各组大鼠血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、清蛋白(Alb)、总胆红素(Tbil)以及肝组织中羟脯氨酸(Hyp)和内皮素-1(ET-1)的水平,肠系膜上静脉插管测定门静脉压力,观察肝组织病理形态的变化,并与模型组比较。[结果]治疗组门静脉压力明显降低,血清ALT、AST、Tbil及肝组织Hyp和ET-1水平与模型组比较均显著下降,病理学显示治疗组基本恢复正常。[结论]肝硬化时肝组织中ET-1显著升高;SA-B能显著降低肝硬化时升高的门静脉压力和肝组织中ET-1的水平。     

甘氨酸加压素和血管加压素减轻肝硬化门脉高压性胃病患者胃充血

本文旨在研究血管加压素和人工合成的血管加压素衍生物甘氨酸加压素(glypressin)对肝硬化门脉高压性胃病(PHG)患者胃粘膜灌注量的影响。 病人和方法:PHG患者28例,均经内镜     

脾切除对原发性胆汁性肝硬化小鼠肝组织纤维化影响研究

目的探讨脾切除对原发性胆汁性肝硬化(PBC)小鼠的影响及其相关因素。方法 40只雌性C57BL/6小鼠被分为脾切除组(n=10)、假手术组(n=10)、模型组(n=10)和正常对照组(n=10)。在前三组,采用1%聚肌胞苷酸腹腔注射建立PBC模型,在正常对照组,给予等体积生理盐水腹腔注射。在实验20 w末,对动物分别行脾切除术,或在假手术组采取腹壁切开后仅轻微翻动脾脏,或在模型组和正常对照组不行任何处理。在实验32w,行血生化和肝组织病理学检查。采用RT-PCR法检测肝组织转化生长因子-β1(TGF-β1)及其Ⅰ型受体(TβRI)和Ⅱ型受体(TβRII)mRNA水平。取末端回肠组织,采用ELISA法检测其匀浆TNF-α水平。结果在32w时,脾切除组、假手术组和模型组动物肝指数均显著低于对照组[(41.5±5.2)、(39.6±7.5)、(39.1±1.0)对(53.2±2.1),P值均0.05];脾切除组血清ALT、AST和ALP水平分别为(43.5±6.4) U/L、(157.7±20.9) U/L和(178.1±38.0)U/L,显著低于模型组[(52.0±9.0) U/L、(183.4±12.4) U/L和(195.3±62.6) U/L,P值均0.05];脾切除组肝组织纤维化程度明显轻于假手术组和模型组;脾切除组肝组织TGF-β1、TβRI和TβRII mRNA水平分别为(0.5±0.09)、(0.5±0.05)和(0.5±0.09),显著低于模型组[(1.0±0.10)、(1.0±0.08)和(1.0±0.09),P值均0.05];脾切除组回肠末端匀浆TNF-α水平为(50.0±8.6) ng/L,显著低于模型组[(106.8±19.8) ng/L,P0.05]。结论脾切除可缓解PBC小鼠肝组织纤维化进程,可能与抑制肝脏TGF-β1表达和抑制回肠末端TNF-α分泌有关。     

Effects of calcium antagonists on hepatic and systemic hemodynamics in awake portal hypertensive rats

The effects of the calcium antagonists diltiazem and nicardipine on portal pressure and splanchnic blood flow were studied in awake, unrestrained portal hypertensive rats. Portal hypertension was induced in rats by partial portal vein ligation. Hemodynamic measurements were done using the radiolabeled microsphere technique. In portal veinligated and sham-operated rats, intraarterial diltiazem and nicardipine reduced mean arterial pressure. No significant changes, however, were observed in portal pressure and cardiac index. In portal vein-ligated rats, diltiazem and nicardipine increased portal tributary blood flow. Portal tributary vascular resistance was also significantly decreased. The decrease in the hepatocollateral vascular resistance prevented an increase in portal pressure. In sham-operated rats, these changes were not observed. It is possible that the vascular responses to calcium antagonists are altered in portal vein-ligated rats. These findings demonstrate that the hemodynamic effects of calcium antagonists occur at two levels. First, the increase in portal tributary blood flow appears to be a selective effect on portal tributary vascular resistance. Secondly, the portal pressure does not increase in parallel with the increase in portal tributary blood flow because of a similar reduction in portocollateral vascular resistance.     

Effect of parathyroid hormone on portal pressure in portal hypertensive rats

Conflicting results have been common in the pharmacological treatments of portal hypertension. In an attempt to seek better management of portal hypertension, we studied the effect of the synthetic parathyroid hormone (PTH) fragment, [bPTH-(1-34)], in portal hypertensive rats (partial portal vein ligation). PTH, 10 U/kg, administered via the jugular vein resulted in a reduction of both mean arterial blood pressure (MAP) and portal pressure (PP) to a similar extent (18.9% and 16.9%, respectively). A higher dose (40 U/kg) of PTH lowered the PP by 27.8% and MAP by 43.2%. Hemodynamic experiments, performed with labelled microspheres, demonstrated that PTH decreased the blood flow of the splanchnic and hepatic portal collateral vascular beds. To determine whether there is a direct vasodilatory effect on the venous vasculature, the effect of PTH on the isolated portal vein was examined. PTH was capable of inhibiting both spontaneous and drug (methacholine 10(-7) mol/l or KCl 40 mmol/l-induced contraction in a dose-dependent manner. Therefore, it can be assumed that some of the effect of PTH on portal pressure is due to a selective effect on the portal vein.     

门高压鼠血浆前列环素与门脉压力的关系

目的 探讨门脉压力升高和门体分流在前列环素（ＰＧＩ２）或高中的作用。方法 ３６只雄性ＳＤ大随机分为四组：肝前型（ＰＨＰＨ，ｎ＝８）和肝内型门高压（ＩＨＰＨ，ｎ＝９），端侧门腔分流（ＰＣＳ，ｎ＝８）以及手术对照组（ＳＯ，ｎ＝１１），模型制备后２周；（１）测游离门脉压（ＦＰＰ）；（２）应用核素微球技术研究全身及内脏血流血压学；（３）从股动脉采集血样用放射免疫法测血浆６－酮－前列腺素Ｆ１α（６－ｋｅｔｏ     

Glytan decreases portal pressure via mesentery vasoconstriction in portal hypertensive rats

AIM: To investigate the effects of Glytan on splanchnic hemodynamics and its reduction of portal pressure in portal hypertensive rats.METHODS:Glytan(Ganluotong in Chinese),is composed of salvianolic acid B and diammonium glycyrrhizinate.Portal hypertension(PHT)was induced in the rats by common bile duct ligation(BDL).Hemodynamic studies were performed using the colored microsphere method.Radioimmunoassay(RIA)was used to determine endothelin(ET)-1 levels in the mesenteric circulation.Western blotting methods were used to investigate the effect of Glytan on ET A receptor(ETAR),ET B receptor(ETBR),endothelial NO synthase(e NOS),G-protein-coupled receptor kinase(GRK)2,and β-arrestin 2 expression in the mesentery.The m RNA of ETAR and ETBR was determined using real-time polymerase chain reaction.RESULTS:Treatment with Glytan reduced portal pressure(PP)and portal territory blood flow(PTBF)and increased both mean arterial pressure(MAP)and splanchnic vascular resistance(SVR).Especially at 4wk,PP decreased by about 40%,while MAP increased by 13%,SVR increased by 12%,and PTBF decreased by about 21%.The effect of blood flow reduction was greatest in the mesentery(about 33%)at 4 wk.The mesenteric circulation ET-1 levels of BDL rats were lower and negatively correlated with PP at 4 wk.Glytan can increase mesenteric ET-1 content and inhibit ETBR,e NOS,GRK2,andβ-arrestin 2 expression in the mesentery.Moreover,Glytan showed no effect on the expression of ETAR protein and m RNA.CONCLUSION:The decreased PP and PTBF observed after Glytan treatment were related to increased mesenteric vasoconstriction and increased receptor sensitivity to vasoconstrictor.     

双剂量奥曲肽对肝硬化门脉高压症断流术后患者血流动力学的影响

目的研究双剂量奥曲肽对肝硬化门脉高压症断流术后患者门脉压力、肝脏血流动力学影响。方法肝硬化门脉高压症断流术患者26例,随机分两组,术后24h开始用奥曲肽。A组12例,奥曲肽50μg／h;B组14例,奥曲肽25μg／h;胃网膜右静脉插管至门静脉主干,动态测定门脉压力;彩色超声多普勒测定门脉直径（PV）、门脉最大血流速度（PFVmax）、门脉平均血流速度（PFVmean）、肝动脉最大血流速度（HAVmax）、肝动脉最小血流速度（HAVmin）;计算门脉血流量参数（PFI）、肝动脉血流量参数（HAFI）。结果断流术后,两组患者门脉压力平均降幅15．4％,PFI降低（P〈0．05）;HAVmax、HAVmin、HAFI增加（P〈0．05）。用奥曲肽72h后,两组PFI、PFVmax、PFVmean降低（P〈0．05）;用药5min门脉压力降低,24h达高峰,门脉压力平均降幅20．6％。A组停药后48h内,门脉压力未见回升,平均降幅23．1％;B组停药后2h门脉压力有回升趋势,平均降幅11．6％;停药后24h、48h两组患者门脉压力比较差异有统计学意义（P〈0．01）。Logistic分析发现,PV、PFVmax、PFVmean、HAVmax、HAVmin与门脉压力无独立相关性。结论肝硬化门脉高压症患者行断流术后,门脉压力降低。双剂量奥曲肽均能明显降低门脉压力;停药后48h内,奥曲肽50μg／h组门脉压力未见回升。提示,临床用奥曲肽50μg/h对防止静脉曲张再出血更合理。     

Sustained reduction of portal pressure by administration of octreotide-LAR in portal hypertensive rats

Objective: Recent studies have demonstrated octreotide as being potentially beneficial for the long-term management of cirrhotic portal hypertension. However, its short-term effects, requiring subcutaneous administration at least twice daily, make it inconvenient, practically, for long-term therapy. Hence, the current study was undertaken to evaluate the effects of the new long-acting-release octreotide formulation (octreotide-LAR) on portal pressure in a prehepatic portal hypertensive rat model. Methods: 14 days after portal vein stenosis or sham operation, rats were treated with either octreotide-LAR (0.25 mg/kg body weight, subcutaneously) or vehicle, after the baseline portal pressure measurements were obtained in each group. On days 10, 15, 18, 21, 24, 27 and 30 post-treatment, eight rats from each sub-group (portal vein stenosis plus octreotide-LAR, or vehicle, sham-operated plus octreotide-LAR or vehicle) were subjected to portal vein pressure measurement. Results: portal vein-stenosed rats exhibited a significantly higher portal vein pressure than sham-operated rats (13.82±2.18 vs. 5.82±1.08 mmHg, P=0.0001). Octreotide-LAR treatment was found to significantly (P=0.001) reduce portal pressure in portal vein stenosed rats from the tenth post-injection day and thereafter to sustain reduction. Conclusion: the long-acting-release octreotide given in a single dose in a prehepatic portal hypertensive rat model diminishes and sustains diminished portal pressure for 20 days after the tenth post-injection day. These findings seem promising for the portal hypertensive patient and further clinical studies are necessary.     

The role of portal pressure in the severity of bleeding in portal hypertensive rats

The aim of this study was to investigate the role of portal hypertension determining the severity of bleeding in portal hypertensive rats. The effects of section of branches of the ileocolic vein were studied in sham-operated (SO), partial portal vein-ligated (PPVL), and common bile duct-ligated (CBDL) rats. The ensuing hemorrhage was compared with that caused by section of femoral vein, where the portal hypertensive factor is excluded. In PPVL rats, section of branches of increasing size (divided into fourth, third, second, and first order) resulted in increasingly severe bleeding (arterial pressure: / +/- 4%, / 6 +/- 12%, / /15 +/- 8%, and / 28 +/- 13%; P <.005; hematocrit / 4 +/- 2%, / 6 +/- 1%, / 7 +/- 2%, and / 10 +/- 4%; P <.005). Bleeding from first-order branches was mild in SO, moderate in PPVL, and severe in CBDL rats, as shown by increasing changes in arterial pressure (/ 3 +/- 3%, / 12 +/- 16% and, / 43 +/- 23%; P <.01), hematocrit (/ 4 +/- 1%, / 12 +/- 2%, and / 32 +/- 19%; P <.01), and mortality (0%, 0%, and 56%; P <.001). Greater blood loss in CBDL rats was associated with higher portal pressure (16.6 +/- 2.7 vs. 13. 1 +/- 1.1 mm Hg in PPVL; P <.01) and more prolonged bleeding time (70 +/- 4 vs. 35 +/- 3 seconds in PPVL; P <.001). Vessels were similarly dilated in CBDL and PPVL (0.7 +/- 0.2 and 0.7 +/- 0.1 vs. 0.4 +/- 0.1 mm in SO; P <.05). Section of femoral vein caused equal blood loss in SO, PPVL, and CBDL rats, assessed by falls in hematocrit (/ 8 +/- 2%, / 7 +/- 1%, / 8 +/- 1%, respectively; NS) and by the blood loss (3.6 +/- 0.7, 3.5 +/- 0.9, and 3.8 +/- 0.7 g; NS). The study shows that the degree of portal pressure elevation is a major determinant of the severity of portal hypertension-related bleeding in PPVL and CBDL rats.