加味瓜蒌散对肝硬化门静脉高压症患者胃肠激素、肝纤维化指标和血流动力学的影响

目的:观察加味瓜蒌散对肝硬化门静脉高压症患者胃肠激素、肝纤维化指标和血流动力学的影响.方法:选择符合2000年9月西安全国传染病与寄生虫病学术会议<肝硬化诊断标准>同时符合中医血瘀阻络证型肝硬化门脉高压症患者40例,随机分治疗组和对照组.两组患者均常规接受护肝、降酶等对症治疗,治疗组患者加服加味瓜蒌散,对照组患者加服心得安(通用名普萘洛尔).治疗前后清晨空腹取血放射免疫法测胃肠激素胃动素(MTL)、胃泌素(GAS)、胰高血糖素(GLU)、脑肠肽(SS),肝纤维化指标透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(C-Ⅳ)、层粘连蛋白(LN),并进行血流动力学检查.结果:治疗组治疗后GAS、MTL水平明显下降(P＜0.01或P＜0.05),HA、PCⅢ、C-Ⅳ、LN下降(P＜0.01或P＜0.05),门静脉内径、血流量与用药前比较差异有显著性意义(P＜0.05),血流速度治疗前后与对照组比较差异无显著性意义(P＞0.05).结论:加味瓜蒌散能够有效调节肝硬化门静脉高压症患者胃肠激素、血流动力学,降低纤维化指标,延缓门脉高压的形成,减轻门脉高压性胃病的程度,减少食管胃底静脉曲张破裂出血的机会及风险,疗效优于心得安,是防治肝硬化门脉高压症的有效方剂.     

门静脉宽度测量作为评价心得安对门脉高压疗效的价值

目的探讨门静脉宽度测量作为评价心得安治疗门脉高压的价值。方法将我院2000—01／2005-01收治的102例肝硬化失代偿期病人随机分成两组，心得安组54例，对照组48例。两组治疗前后分别进行肝功能化验及B超测量门静脉宽度，比较其变化是否有差异。结果心得安组治疗后肝功能改善及门静脉宽度缩小与对照组比较有显著性差异（P〈0．01），提示门静脉宽度测量可作为评价心得安治疗门脉高压疗效的简易指标。     

复方丹参注射液对糖尿病胃肠病变患者胃肠激素的影响

将115例2 型糖尿病合并胃肠病变患者随机分为两组,治疗组给予复方丹参注射液250ml静滴、1次/d,共15 d;对照组给予维生素B1100mg和维生素B12.250μg 肌肉注射、1次/d,共15 d.发现治疗组消化不良、食欲减退、便秘或腹泻的好转率明显优于对照组,胃肠排空实验较对照组明显缩短.治疗组治疗前后促胃液素、胃动素、胰高血糖素、胃排空时间均有统计学差异.提示复方丹参注射液可改善糖尿病胃肠病变的症状、体征,使胃排空时间缩短、胃肠激素接近正常,且无副作用,值得临床推广.     

加味瓜蒌散对门静脉高压症大鼠门静脉压力与肝纤维化指标的影响

目的:观察加味瓜蒌散对门脉高压大鼠门静脉压力、肝纤维化指标的影响。方法:采用M ed lab-Ug4Cs生物信号采集处理系统、放免法,检测正常组、模型组、心得安对照组、加味瓜蒌散治疗组大鼠门静脉压力、肝纤维化指标。结果:模型组大鼠门静脉压力较正常组明显升高(P<0.01),加味瓜蒌散各剂量组、心得安对照组大鼠门脉压力较模型组明显下降(P<0.01),加味瓜蒌散各剂量组大鼠门脉压力与心得安治疗组比较,差异无显著性意义(P>0.05)。加味瓜蒌散各剂量组大鼠Ⅳ-C、PCⅢ、HA、LN与模型组比较均明显下降(P<0.01或P<0.05);而心得安组大鼠Ⅳ-C、PCⅢ、LN与模型组比较,差异无显著性意义(P>0.05),而HA明显升高(P<0.05)。结论:加味瓜蒌散能有效降低门静脉压力,在改善肝纤维化指标方面优于心得安。其作用机制可能与其良好的抗肝纤维化、阻止肝硬化形成、降低门脉压力、改善肝功能的作用有关。     

丹参对门脉高压大鼠胃粘膜及肝脏的影响

用丹参对肝硬变门脉高压大鼠进行了治疗，并与心得安进行了比较。结果表明，丹参和心得安均可使门脉压力下降，胃粘膜前列腺素Ｅ２含量、胃粘膜血流量和胃壁结合粘液量增加。但心得安使肝细胞坏死加重，血清ＡＬＴ和ＴＢ不能降低，ＡＬＴ反有升高。而丹参可使肝细胞损害减轻，肝内纤维组织减少，ＡＬＴ、ＡＬＰ和ＴＢ降至正常水平。说明心得安虽可使门脉高压性胃粘膜病变改善，却可加重肝损害。而丹参不仅可使胃粘膜病变改善，而且还能改善肝功，促进肝纤维吸收。     

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.     

中药泻心汤对大鼠胃排空和胃肠激素的影响

目的:观察半夏泻心汤(BX)、生姜泻心汤(SJ)和甘草泻心汤(GC)对大鼠胃排空及胃肠激素的影响.方法:60只SD大鼠随机分为正常对照组(n=15)、半夏泻心汤组(n=15)、生姜泻心汤组(n=15)和甘草泻心汤组(n=15),大鼠连续灌胃7d,半夏、生姜和甘草泻心汤组给药量分别为5.67,7.42,5.36g/(kg?d);通过测定大鼠胃内标记物-葡聚糖蓝的相对残留率来观察胃排空能力;采用放射免疫学的方法测定大鼠血中胃肠激素的含量。结果:与正常对照组(99.9%±32.2%)相比,半夏泻心汤组(66.1%±21.1%,P=0.014)胃内色素相对残留率明显减少,生姜泻心汤组(141.8%±21.07%,P=0.012)胃内色素相对残留率明显增加,甘草泻心汤胃排空作用不明显.与正常对照组相比,半夏泻心汤组的血管活性肠肽(VIP)、P物质(SP)水平下降显著(348.1±102.5ng/Lvs445.8±101.9ng/L,P=0.032;47.0±15.2ng/Lvs63.0±14.7ng/L,P=0.011);半夏、生姜泻心汤组生长激素(SS)水平明显升高(562.3±149.7,553.9±98.9ng/Lvs461.7±77.0ng/L,P=0.014和P=0.023);生姜、甘草泻心汤组胃泌素(GAS)水平(70.7±11.9,79.7±9.3ng/Lvs56.0±11.5ng/L,P=0.011和P=0.001)、胃动素(MTL)水平(205.0±22.0,205.1±43.1ng/Lvs162.6±19.5ng/L,P=0.001和P=0.014)显著升高.结论:三泻心汤对大鼠胃排空及胃肠激素的影响存在差异,可能是三方功能主治差异的原因之一.     

强肝软坚汤与心得安联合治疗肝硬化门脉高压症临床观察

对110例肝硬化门脉高压症患者随机分组,前瞻性研究强肝软坚汤、心得安及强肝软坚汤与心得安联合用药三组临床疗效,结果联合用药组疗效优于单独用药二组(P<0.01)。提示强肝软坚汤与心得安二者不同的治疗机制,对肝硬化门脉高压症可起到协同治疗效果。     

洛赛克、果胶铋、心得安治疗门脉高压性胃病疗效观察

本组82例门脉高压性胃病病人，均为住院病人，男性68例，占82．9％，女性14例，占17％；年龄在18～65岁，平均年龄41岁。肝炎后肝硬化73例，酒精性肝硬化9例，全部病例都具有肝硬化门脉高压征的临床表现，腹胀消化不良68例，呕血和黑便35例，返酸18例，腹水征67例，实验室检查肝纤维化四项指标异常82例，血浆白蛋白低，白球比例倒置65     

肝硬化门脉高压症与胃肠动力异常

肝硬化门脉高压症可引起食管及胃肠动力异常,而胃肠动力异常又可使肝硬化门脉高压症的病情进一步加剧,甚至导致严重并发症。     

Effects of propranolol on venous compliance in conscious rats with pre-hepatic portal hypertension

BACKGROUND/AIMS: The venous system is the primary capacitance region in the body. However, the influence of active changes in the venous system on the hemodynamic alterations of portal hypertension is poorly understood. To investigate venous compliance (VC) in conscious partial portal vein ligated rats (PPVL) and the effect of propranolol on VC. METHODS: Venous compliance was derived from the relationship between changes in mean circulatory filling pressure (MCFP) and changes in blood volume (BV). Measurements were performed before and after i.v. propranolol (7.5 mg/Kg) or placebo in rats with portal hypertension due to PPVL and sham operated controls. RESULTS: PPVL rats had an increased VC when compared to Sham (4.9+/-1.4 vs. 3.7+/-0.9 ml kg-1 mm Hg-1; P<0.02). VC did not change after placebo but was significantly reduced by Propranolol in PPVL (-32.9+/-15.7%; P<0,007). Propranolol did not modify venous compliance in sham operated rats (+10.9+/-13.4%; P=ns). CONCLUSIONS: Venous compliance is increased in portal hypertensive rats, suggesting that the venous system contributes to the profound circulatory changes encountered in portal hypertension. The increased venous compliance is markedly attenuated by propranolol, suggesting that this abnormality is related to increased adrenergic activity.     

Short-term effects of propranolol on portal venous pressure

The present study was designed to investigate the effect of propranolol on portal pressure of patients with alcoholic cirrhosis and portal hypertension and to correlate these effects with clinical and laboratory parameters. The mean baseline hepatic venous pressure gradient in the 50 patients studied was of 18.2 +/- 4.1 mm Hg. It decreased significantly 2 hr after the oral administration of 40 mg of propranolol to 15.7 +/- 4.2 mm Hg (a mean reduction of 13.4 +/- 17%). This reduction in hepatic venous pressure gradient resulted mainly from a decrease in mean wedged hepatic venous pressure. There was no correlation between the decrease in hepatic venous pressure gradient and the decrease in heart rate. When results were analyzed individually, only 15 (30%) showed a large decrease in hepatic venous pressure gradient (greater than 20%), 15 (30%) showed a moderate decrease (10 to 19%), and in 20 patients (40%) there was no reduction or an increase in hepatic venous pressure gradient. Comparison of "responders" (those that reduced hepatic venous pressure gradient greater than 10%) and "nonresponders" (hepatic venous pressure gradient reduction less than 10%) showed no significant differences in baseline laboratory and hemodynamic parameters, in the severity of the liver disease, in the heart rate and blood pressure response to propranolol, nor in the propranolol plasma levels achieved 2 hr after propranolol administration. Propranolol plasma levels correlated with the reduction in heart rate but not with the reduction in hepatic venous pressure gradient. Of 14 nonresponders to 40 mg of propranolol who received additional doses, six showed a reduction in hepatic venous pressure gradient.(ABSTRACT TRUNCATED AT 250 WORDS)     

卡维地洛与普萘洛尔降低肝硬化门静脉高压患者肝静脉压力梯度效果的对比分析

目的探讨卡维地洛和普萘洛尔降低肝硬化门静脉高压患者肝静脉压力梯度(HVPG)的幅度、应答率以及用药后不良反应的差异,对卡维地洛降低门静脉压力的有效性和安全性进行评价。方法收集2010年10月-2012年1月在山东大学附属省立医院确诊的64名肝硬化门静脉高压患者,随机分为2组:普萘洛尔组(n=33)和卡维地洛组(n=31),根据血压和心率调整剂量,疗程7 d,均于治疗前后行HVPG测定及肝肾功能指标检测,比较2组患者HVPG降低的幅度及应答率,并观察患者低血压、腹水、肾损伤等不良反应的发生情况。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验或Fisher精确概率法。结果卡维地洛组和普萘洛尔组的HVPG均明显降低,降低幅度分别为(28.30±22.19)%和(12.38±24.09)%,其中卡维地洛组降低更明显,差异有统计学意义(t=0.223 4,P=0.032)。2组应答率分别为:卡维地洛组56.7%(17/30),普萘洛尔组41.9%(13/31),2组差异无统计学意义(χ2=1.324,P=0.250)。卡维地洛组平均动脉压的降低较普萘洛尔组明显,差异有统计学意义(t=2.338,P=0.024),但患者未出现明显低血压的不良反应;2组患者胆红素、血肌酐和尿素氮在治疗前后无明显升高,亦无腹水生成或加重的趋势。结论本研究提示在短期内卡维地洛降低HVPG的作用较普萘洛尔显著,且无明显不良反应;其用于肝硬化门静脉高压的治疗是安全有效的。     

Discrepancy between wedged hepatic venous pressure and portal venous pressure after acute propranolol administration in patients with alcoholic cirrhosis

In patients with alcoholic cirrhosis, wedged hepatic venous pressure closely reflects portal venous pressure. This study was carried out to determine if propranolol-induced reductions in portal venous pressure are accurately evaluated by the measurement of wedged hepatic venous pressure. Hepatic venous cannulation and percutaneous transhepatic catheterization of the portal vein were simultaneously performed in 7 patients with alcoholic cirrhosis. One hour after oral administration of 40 mg of propranolol, wedged hepatic and portal venous pressures significantly decreased from 24.3 +/- 3.5 (mean +/- SD) to 19.0 +/- 3.0 mmHg, and from 24.7 +/- 3.9 to 22.4 +/- 3.6 mmHg, respectively. Although no significant difference was found between baseline wedged hepatic and portal venous pressures, a significant difference was found between these pressures after propranolol administration. We concluded that during acute administration of a drug acting on the splanchnic circulation, the measurement of wedged hepatic venous pressure may not provide a reliable estimation of the magnitude of the changes in portal venous pressure. There is, however, no evidence that the direction of the changes might not be adequately assessed by wedged hepatic venous pressure measurement.     

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.     

肝硬化门静脉高压对D-木糖吸收率的影响及意义

目的:评价D-木糖吸收率在肝硬化门静脉高压进程中的变化规律,欲探索一种非损伤性且简便实用的推测门静脉压力的方法.方法:SD大鼠80只,♂,体质量180-220 g,随机分为:正常组5只,正常饮水,正常饮食.肝硬化门脉高压诱导组75只,共成模55只,前5wk使用0.03%硫代乙酰胺,后5 wk使用0.04%硫代乙酰胺作为其饮水,停药后6wk仍继续观察肝组织及门静脉压力变化.正常组及第2、4、6、8、10、11、12、13、14、15、16周共12组,对每组大鼠检测D-木糖含量及门静脉压力,并计D-木糖吸收率与相应的门静脉压力的相关性.结果:在肝硬化进程中自第8周纤维间隔明显增生,肝小叶结构紊乱,部分可见假小叶,同时门静脉压力及D-木糖吸收率也是自第8周开始同步出现显著性差异.D-木糖吸收率与门静脉压力呈负相关,具有统计学意义(r=-0.697,P<0.01),同时得出两者的直线关系方程:y=-0.01x+0.2791.结论:D-木糖吸收率可以反映肝硬化门静脉压力的变化趋势,对于临床上判断门静脉压力的大小、评价治疗效果具有重要意义.     

The hypotensive effect of oral nitroglycerin on portal venous pressure in patients with cirrhotic portal hypertension

Abstract Nitroglycerin was administered orally to seven patients with cirrhosis and portal hypertension, to determine whether portal venous pressure (PVP) may be lowered without the systemic effects associated with its intravenous or sublingual use. PVP was measured via direct cannulation of the portal vein transhepatically using a Chiba needle. PVP decreased from 29 (s.d. = 4) to 22.7 (s.d. = 3.7) mmHg (22% mean fall) following 1.2 mg nitroglycerin with onset 7–15 min following ingestion, and the response persisted for up to 150 min. This was not associated with headache in any patient. Although a decrease in blood pressure was seen in most patients, this temporally followed the fall in PVP suggesting that it was a secondary response. Sublingual nitroglycerin was given to two patients without change in PVP yet both experienced severe headache. These findings support the hypothesis that oral nitroglycerin is delivered differentially to the portal venous bed with differential effects on PVP. Further studies are needed to evaluate this agent and this strategy for their potential role in long-term control of portal pressure.     

Effect of sublingual isosorbide dinitrate in portal hypertension

Nitrates decrease portal pressure by decreasing portal venous inflow and resistance. We studied over 20 minutes the effect of 10 mg isosorbide dinitrate sublingual on intrasplenic pulp pressure, mean arterial pressure and heart rate, in 13 patients with cirrhotic or non-cirrhotic portal hypertension. The pulp pressure fell progressively over 20 minutes, from mean 43.6 +/- 2.4 (SEM) to 35.6 +/- 1.8 cm H2O (p less than 0.001). This was accompanied initially by a significant fall in mean arterial pressure (85.8 +/- 1.9 to 80.4 +/- 2.7 mmHg at 4 minutes; p less than 0.01) and rise in heart rate (92.5 +/- 5.0 to 102.6 +/- 5.9 per minute at 6 minutes; p less than 0.02), following which these parameters remained stable. One patient developed giddiness due to hypotension at 15 minutes. We conclude that sublingual isosorbide dinitrate decreases pulp pressure in cirrhotic and non-cirrhotic portal hypertensives, but this is initially accompanied by significant hemodynamic changes.