肝内型门静脉高压症大鼠内脏高动力循环状态

应用同位素标记的微球测定血流量和门－体分流的技术，检测ＣＣ１４肝硬化大鼠所致内脏和全身血液动力学变化。全部肝硬变大鼠都出现门静脉高压症（门静脉压力１．６５７±０．０６６，对照组１．２２３±０．０３６ｋＰａ；Ｐ＜０．００１）；门－体分流明显增高，但变异大（３５％±２５％，对照组０．３４±０．１６％；Ｐ＜０．０５），范围在３％～８２％间；门静脉血流量增加（７．３３±１．３，对照组６．２８±０．１８ｍＩ。ｍｉｎ－１·１００ｇＢＷ－１；Ｐ＜０．０５）；内脏血管阻力下降（０．６１±０．１４，对照组０．９±０．１９ｋＰａ·ｍ１－１·ｍｉｎ－１；Ｐ＜０．０１）；门静脉阻力未见明显增高（０．０７８±０．０１，对照１ｌｌ０．０７３±０．Ｏ０７ｋＰａ·ｍ１－１·ｍｉｎ－１；Ｐ＞０．０５）．肝硬变大鼠内脏血液动力学变化表明，门静脉高压症的维持，至少部分取决于高动力的门静脉循环，提供了肝内型门静脉高压症内脏循环高动力状态、门静脉血流量增加的定量资料。     

门静脉高压症血流动力学改变的发病机理

门静脉高压症（PHT）与肝内循环、体循环和门体侧支循环的血流动力学改变有关。肝内阻力增加和高动力循环侧支血管的扩张在门静脉高压的发病机理中起到了重要作用。不同严重程度的肝硬化均存在能广泛影响人体的血流动力学紊乱。门静脉高压和高动力循环是肝硬化患者发病和死亡的主要原因。而血管结构重塑和血管新生是治疗门静脉高压症的重要目标。     

大鼠肝前型门脉高压症形成中门静脉结构的动态变化

目的探讨大鼠肝前型门脉高压症形成中门静脉血管结构的动态变化及意义。方法以部分门静脉结扎（PVL）法复制肝前型门脉高压症大鼠模型，采用组织形态学方法及计算机图像分析技术测定PVL术后1、2、4、8、12、16、20、26天大鼠的门静脉内径（ID）、外径（OD）、壁厚（WT）、壁面轵（CSA）及平滑肌含量（SMC），同步监测大鼠门静脉压力（PVP）、门静脉血流量（PVF）、平均动脉压（MAP）、门静脉阻力（PVR）、内赃血管阻力（SVR）等血液动力学参数的动态变化。结果PVL术后，大鼠的PVP、PVR、SVR、MAP发生了显著变化。PVL大鼠门静脉CSA从术后12d起，ID、OD、WT和SMC从术后16d起较对照组显著增加（P〈0．05）。结论门脉高压大鼠存在高动力循环状态（HCS）。HCS可引起门静脉结构变化，其管壁增厚，内外管径增大，平滑肌增生。     

肝损伤小鼠肝组织氧化／抗氧化平衡的变化及其与TXA2／PGI2？…

目的：探讨氧自由基（ＯＦＲ）及ＴＸＡ２－ＰＧＩ２在实验性肝损伤中的作用。方法：检测肝损伤小鼠肝组织过氧化脂质（ＬＰＯ）、超氧化物歧化酶（ＳＯＤ）含量以及血浆ＴＸＡ和ＰＧＩ２浓度。结果：与对照组比较肝损伤小鼠ＬＰＯ明显升高、ＳＯＤ明显降低，当归可逆转ＬＰＯ和ＳＯＤ的变化；肝损伤小鼠血浆ＴＸＢ２高于对照组，其浓度与肝细胞ＬＰＯ含量呈正相关（ｒ＝０．９５，Ｐ〈０．０１）。结论：ＯＦＲ与ＴＸＡ２／ＰＧＩ２     

门静脉高压症栓塞治疗前、后门静脉压力变化及其临床意义

目的:观察门静脉高压症(PHT)出血患者食管胃底静脉丛应用α-氰基丙烯酸烷基酯(TH胶)栓塞前、后门静脉系统压力动态变化,分析其与消化道出血的关系及预测再出血风险.方法:35例食管胃底静脉曲张破裂出血患者,其中25例行食管胃底静脉丛TH胶栓塞,10例行食管胃底静脉丛TH胶栓塞+部分脾动脉栓塞(PSE).比较术前、术后门静脉主干、肠系膜上静脉、脾静脉压力变化;观察患者术前、术后肝功能变化;观察手术并发症并对患者进行术后随访3～18个月.结果:35例患者均成功止血.食管胃底静脉丛栓塞术后门静脉主干静脉压为(37.45±5.11)am H2O(1 cm H2O=0.098 kPa),较术前明显升高[(32.54±5.23)cm H2O,P<0.01];术后肠系膜上静脉压为(34.33±4.68)cm H2O,较术前升高[(31.46±4.35)am H2O,P<0.053.10例经食管胃底静脉丛栓塞+PSE治疗后,患者门静脉主干、肠系膜上静脉和脾静脉压力均较术前明显降低[分别为(28.70±4.58)cm H2O比(32.68±4.89)cm H2O、(28.03±4.12)cm H2O比(31.46±4.35)cm H2O和(28.81±5.12)cm H2O比(32.89±4.79)cm H2O P值均<0.053.食管胃底静脉丛栓塞术后3周患者血清白蛋白为(34.57±6.84)g/L,较栓塞前高[(30.45±5.78)g/L,P<0.05].术后少量患者出现发热、腹水,经对症治疗后好转.治疗3个月后胃镜显示食管静脉曲张明显减轻.结论:食管胃底曲张静脉栓塞对食管胃底静脉曲张急症出血治疗有效,且对肝细胞功能恢复有一定效果,但有增加消化道再出血风险.食管胃底曲张静脉栓塞+PSE对降低门脉压力及治疗食管胃底静脉曲张出血有效,但不利于肝细胞功能恢复,有增加腹水的风险.     

肝性低氧血症患者血流动力学及血浆中一氧化氮水平变化研究

目的探讨肝硬变门脉高压患者发生低氧血症的机制.方法采用心脏、腹部彩色超声多普勒测定31例肝硬变门脉高压患者和18例正常对照的血流动力学参数,并同时测定血气分析和肺功能及外周血中一氧化氮浓度.结果肝硬变门脉高压患者中14例发生低氧血症(45.16%),肝硬变组肺动脉收缩压(PASP)、血浆中的一氧化氮(NO)均明显高于正常对照组(P=0.0083,P=0.0327),门静脉血流速度(Vp)明显低于正常对照组(P=0.0416),而肺功能无明显改变.结论肝硬变门脉高压患者的全身高动力循环状态导致肺血管功能性或解剖性分流,造成通气与血流比例失调,是导致低氧血症的主要原因,其中一些血管活性物质如NO等可能参与了低氧血症的发生和发展.     

当归对肝硬化门脉高压影响的临床与实验研究

目的和方法：通过对胆管结扎肝硬化犬门脉系压力的直接测定，超声多普勒监测肝硬化患者的门脉血流，研究当归对肝硬化门脉血流动力学的影响。结果：（１）当归静脉给药，肝硬化犬的门静脉压（Ｐｐｖ）、嵌塞肝静脉压（ＷＨＶＰ）、肝静脉压力梯度（ＨＶＰＧ）显著降低（Ｐ＜００５～００１），平均动脉压（ＭＡＰ）、心率（ＨＲ）无明显变化（Ｐ＞００５）；（２）当归口服用药后（１０～１２周），肝硬化患者门静脉内径（Ｄｐｖ）、脾静脉内径（Ｄｓｖ）、脾静脉血流量（Ｑｓｖ）显著降低（Ｐ＜００５～００１），门静脉血流量（Ｑｐｖ）降低无显著意义（Ｐ＞００５）。结论：用药后，患者症状与肝功能（ＡＬＴ）部分好转，未见副作用。表明，当归为降低门静脉高压安全有效的药物     

经颈静脉肝内门体分流术对肝硬化门静脉高压症患者血流动力学的影响

[目的]观察经颈静脉肝内门体分流术(Transjugular intrahepatic portosystemic shunt,TIPS)对肝硬化门脉高压症患者门脉血流动力学的影响,探讨TIPS治疗肝硬化门脉高压症的有效性及机制。[方法]30例肝硬化门脉高压症患者,TIPS术前及术后,彩色多普勒超声测量门脉主干压、内径、血流速度及脾静脉内径。放射免疫法测定血浆肾素(PRA)、血管紧张素Ⅱ(ATⅡ)和血管内皮素(ET)浓度。[结果]30例患者术后的门脉压(24.8±3.6)cmH2O(1 cmH2O=0.098 kPa)与术前的(44.6±5.8)cmH2O比较;门脉内径(1.28±0.06)cm与术前的(1.65±0.09)cm比较;门脉血流速度(43.5±13.2)cm/s与术前的(11.6±3.8)cm/s比较;脾静脉内径(0.92±0.06)cm与术前的(1.24±0.04)cm比较,均P<0.01。血浆ET、PRA、ATⅡ浓度分别为(84.52±28.15)、(89.92±35.46)、(159.65±62.42)ng/L,与术前的(126.25±40.36)(、186.32±68.74)、(253.48±106.57)ng/L比较,均P<0.01。术后腹水较术前明显减少。[结论]TIPS能有效降低门脉压,降低血浆ET、PRA及ATⅡ的浓度,改善患者门脉系统及全身的血循环。     

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.     

丹参等活血化淤中药对门脉高压血流动力学影响的临床与实验研究

目的探讨丹参、当归等及硝苯啶对门脉高压血流动力学的影响。方法采用血管插管测定胆管结扎肝硬化犬门脉系统压力变化；超声多普勒观测肝硬化患者门脉血流动力学变化。结果（１）静脉滴注丹参、当归后，肝硬化犬门静脉压（Ｐｐｖ）、嵌塞肝静脉压（ＷＨＶＰ）、肝静脉压力梯度（ＨＶＰＧ）显著降低（Ｐ＜０．０５～０．０１），平均动脉压（ＭＡＰ）、心率（ＨＲ）无明显变化（Ｐ＞０．０５），硝苯啶则使Ｐｐｖ，ＷＨＶＰ，ＭＡＰ．ＨＲ显著降低（Ｐ＜０．０５）。（２）丹参、丹参＋硝苯啶．丹参＋水＋硝苯啶口服药１０－１２周，能显著降低肝硬化患者门静脉内径（Ｄｐｖ）、脾静脉内径（Ｄｓｖ）．门静脉血流量（Ｑｐｖ），脾静脉血流量（Ｑｓｖ）（Ｐ＜０．０５－０．０１，当归作用较弱。结论对比表明，丹参、当归等中药较硝苯啶对门脉压力作用为慢，但较持久，无副反应。     

Increased Plasma Levels of Corticosterone and Prolactin and Decreased T3 and T4 Levels in Short-Term Prehepatic Portal Hypertension in Rats

Corticosterone, T₃, T₄, and prolactin serum concentrations at 24 hr (N = 10), 15 days (N = 10), and 45 days (N = 10) of postoperative (postop) evolution were assayed to study the neuroendocrine response to portal hypertension. A triple stenosing ligature of the portal vein was used as the surgical technique of portal hypertension. This technique does not produce mortality and causes a decrease in the serum concentrations of T₃ (0.043 ± 0.009 vs 0.55 ± 0.08 ng/ml) and T₄ (3.93 ± 0.55 vs 4.65 ± 0.67 g/ml) and an increase in those of prolactin (28.61 ± 20.20 vs 12.84 ± 3.96 ng/ml) and corticosterone (397.50 ± 64.17 vs 311.53 ± 57.41 ng/ml) at 45 days postop. The T₃, T₄, prolactin, and corticosterone alterations are associated with a persistent increase of TNF- and NO, whose serum concentrations at 45 days postop are, respectively, 1838.33 ± 247.07 vs 48.89 ± 8.75 pg/ml and 0.43 ± 0.13 vs 0.19 ± 0.01 mmol/ml. TNF- and NO could mediate these hormonal alterations in the evolution of short-term portal hypertension in the rat; thus they are involved in the systemic neuroendocrine response that is induced by this injury.     

原发性高血压患者血浆SCUBE1的水平变化及临床意义

目的探讨原发性高血压(EH)患者血浆中新型血小板活化蛋白SCUBE1的水平变化及其与血压的相关性。方法选择2013年12月在石河子大学医学院第一附属医院体检中心筛选的EH患者77例为EH组,选择同期体检的正常健康者75例为对照组。用酶联免疫吸附法检测血浆SCUBE1水平。测定两组血压、腰臀比、体质指数、空腹血糖、总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、尿素氮、肌酐、尿酸等指标。分析SCUBE1与各指标的相关性。结果 EH组血浆SCUBE1水平显著高于对照组(76.95±13.87μg/L比58.34±13.06μg/L,P0.001)。EH组收缩压、舒张压、腰臀比、体质指数、空腹血糖、甘油三酯显著高于对照组(P0.001或P0.05)。相关分析和线性回归分析显示,SCUBE1与收缩压、舒张压呈显著正相关(P0.05)。结论EH患者血浆SCUBE1水平升高。SCUBE1与收缩压、舒张压呈显著正相关。     

Pulmonary Expression of iNOS and HO-1 Protein Is Upregulated in a Rat Model of Prehepatic Portal Hypertension

Portal hypertension is associated with a wide range of pulmonary pathophysiologies, ranging from portopulmonary hypertension to hepatopulmonary syndrome. Although the clinical and pathological features of pulmonary dysfunction in this setting have been extensively characterized, the underlying biology is not well understood. Specifically, the role of mediators that regulate mesenteric vascular hemodynamics in portal hypertension, such as nitric oxide and endothelin, have not been studied in the lung. Using a rat model of prehepatic portal hypertension with preserved hepatic function, we examined pulmonary elaboration of endothelial nitric oxide synthase (NOS), inducible NOS, heme oxygenase- 1 (HO-1), heme oxygenase-2 (HO-2), endothelin-1 mRNA, and protein. In comparison to sham controls, portal hypertensive animals exhibited significantly increased pulmonary iNOS and HO-1 mRNA and protein. Cyclic GMP was significantly increased in portal hypertensive lung tissue, suggesting activation of guanylyl cyclase by the endproducts of iNOS and/or HO-1 activity. Using immunohistochemical analysis, iNOS expression was localized to the vascular endothelium, while HO-1 localized to bronchiolar epithelium and macrophages. These results suggest that production of nitric oxide and carbon monoxide may contribute to the pulmonary pathology associated with portal hypertension.     

呼吸对门脉系统血管内径的影响与门脉高压症相关性的临床研究

研究呼吸对门脉系统血管内径的与门脉高压症的相关性。采用Ｂ型超声探测了伴有门脉高压症的肝炎肝硬化病人的门静脉内径,分别记录在吸气末及呼气末两种状态下的测值,并与对照组进行比较分析,在对照组,当深吸气时,胸廓扩张,回心血量增加,同时门脉血流亦增加,门静脉及脾静脉内径增宽,深呼气时正相反,但是,当门脉内压力增高后,呼吸对 门脉内血流及内径的影响明显减弱。通过Ｂ型超声观察呼吸对门脉血管内径的影响程度对于门     

肝硬化门脉高压患者胰岛细胞早期分泌相的变化

选择肝硬化门脉高压患者（Ｃｈｉｌｄ－Ｐｕｇｈ 分级Ｂ级）２０ 例及健康对照者２０ 例，快速静脉注射左旋精氨酸（Ｌ－Ａｒｇ）２０ｍ ｌ，于注射前及注射后２、４、６ 分钟分别测血清胰岛素（Ｉｎｓ）、Ｃ肽（Ｃ－ｐ）和胰升糖素（Ｇｃ）水平。对照组另行葡萄糖（Ｇｌｕ）兴奋试验，方法同上。结果显示，对照组经葡萄糖和Ｌ－Ａｒｇ 刺激后２ 分钟Ｉｎｓ、Ｃ－ｐ 分泌达峰值，前者峰值虽高于后者，但无明显差异（Ｐ＞ ０．０５）。肝硬化门脉高压组空腹时Ｉｎｓ和Ｇｃ高于对照组（Ｐ均＜ ０．０５），Ｌ－Ａｒｇ 兴奋后２ 分钟两组Ｉｎｓ、Ｃ－ｐ 和Ｇｃ达峰值，门脉高压组Ｉｎｓ和Ｇｃ峰值虽高于对照组，但峰值较空腹值升高倍数却低于对照组（Ｐ均＜ ０．０５）。提示肝硬化门脉高压患者存在胰岛素抵抗、胰升糖素血症及胰岛早期储备能力下降     

Effects of Octreotide on Intestinal Transit and Bacterial Translocation in Conscious Rats with Portal Hypertension and Liver Fibrosis

In cirrhosis, delayed intestinal transit may be responsible for increased endoluminal bacterial overgrowth and increased bacterial translocation. Octreotide has been reported to reduce intestinal transit. Therefore, we evaluated whether octreotide administration influences bacterial translocation in a model of liver fibrosis secondary to dimethylnitrosamine (DMNA) administration. Twenty-nine conscious rats were randomly assigned to three groups (sham rats + placebo as controls, DMNA + placebo, DMNA + octreotide, 1.5 g/kg thrice daily subcutaneously), and including portal pressure, intestinal transit (radioactive method), and bacterial translocation were measured. Three of four variables measuring intestinal transit suggested a significant delay in intestinal transit in DMNA rats compared to controls (eg, cumulated radioactivity 50%: controls: 5.3 ± 1.5, DMNA + placebo: 3.2 ± 1.2, DMNA + octreotide: 2.7 ± 1.9, P < 0.01). This delay tended to be enhanced by octreotide but the effect was only significant with one of the intestinal transit variables. Bacterial translocation was significantly increased in DMNA rats compared to controls but octreotide did not increase translocation [eg, germ count (log) in lymph nodes: controls: 3.1 ± 3.6, DMNA + placebo: 12.3 ± 4.4, DMNA + octreotide: 10.6 ± 6.0, P < 0.001]. There was no significant correlation of portal pressure, intestinal transit, and bacterial translocation in this study. In conclusion, our results show that, although octreotide worsens delayed intestinal transit, it has no influence on the level of bacterial translocation.     

The Mechanism of the Antihypertensive Action of Progesterone: Hemodynamic Studies in Rats with Partial Nephrectomy Salt Hypertension

In order to assess the mechanism of the antihypertensive action of progesterone, its effect on blood pressure, plasma volume, extracellular fluid volume, cardiac output and total peripheral resistance was studied in salt loaded 2/3 nephrectomized rats (one kidney and both poles of the remaining one removed) and in salt loaded rats in which in addition to nephrectomy adrenalectomy was also performed. Administration of progesterone (15 mg/kg, s.c., 3 times a week) during the six week course of salt loading significantly (P > 0.01) lowered blood pressure in both nephrectomized and nephrectomized, adrenalectomized rats. When compared to normal, untreated rats both plasma and extracellular fluid volume were found to be elevated in all nephrectomized salt loaded rats. However, no effect of progesterone on body fluid volumes was noted in either nephrectomized or nephrectomized, adrenalectomized rats. Progesterone lowered blood pressure and total peripheral resistance and had no effect on cardiac output in partially nephrectomized, salt loaded rats. The results indicate that: 1. in partially nephrectomized, salt loaded rats progesterone exhibits its antihypertensive action in the absence of mineralocorticoids, 2. in this hypertensive model progesterone does not     

应激性血压升高对大鼠下丘脑肾上腺髓质素水平的影响

目的 探讨应激性血压升高对下丘脑肾上腺髓质素编码基因表达及水平的影响.方法 58只雄性SD大鼠随机分为对照组(n=23)和应激组(n=35),应激组给予噪声或噪声加足底电击随机组合输出刺激制备应激性高血压动物模型.48只动物在实验第1、5、10、15天以及实验结束后5、10天测量尾动脉压后处死(每个时间点对照组和应激组分别为n=3和n=5).分离下丘脑并制备组织匀浆后分别采用逆转录聚合酶链反应检测肾上腺髓质素编码基因表达变化,放射免疫法检测肾上腺髓质素水平变化.另外10只在实验第10天后断头取下丘脑制备冰冻切片,采用免疫组织化学法检测肾上腺髓质素免疫阳性细胞分布变化.结果 应激5天后动物血压开始明显升高,15天达到高峰(156.3±3.3 mmHg比114.0±2.6 mmHg,P<0.01),应激结束10天血压仍维持在较高水平.与对照组相比较,肾上腺髓质素编码基因mRNA表达在应激10天内逐渐上调(第5天0.99±0.05比0.92±0.04,P<0.05;第10天1.26±0.04比0.92±0.04,P<0.01),而后表达下调,在应激第15天仍高于对照组(1.00±0.04比0.92±0.04,P<0.05).应激结束后5天表达仍高于对照组,但差异无统计学意义;与同时间点对照组相比较,肾上腺髓质素水平在应激10天内逐渐增加(第1天1.25±0.22比0.93±0.19,P<0.05;第5天1.69±0.29比0.97±0.21,P<0.01;第10天2.00±0.28比0.94±0.24,P<0.01).应激组(n=5)大鼠下丘脑室旁核区域肾上腺髓质素阳性细胞的光密度明显高于对照组(n=5),由正常的110.21±3.10增加到127.56±3.50(P<0.01),而其他区域无明显变化.结论 应激性血压升高过程中,下丘脑肾上腺髓质素编码基因mRNA表达和肾上腺髓质素水平均发生相应变化,尤其以室旁核明显,提示下丘脑室旁核肾上腺髓质素可能通过维持血压平衡及内环境稳态参与应激致高血压发生的病理生理过程.     

高血压患者血浆同型半胱氨酸水平与危险分层的关系

目的观察高血压不同危险分层患者血同型半胱氨酸（homocysteine,HCY）水平的变化情况,以探讨高血压患者血HCY值变化的临床意义。方法选择90例住院的高血压患者,按《中国高血压防治指南》（2005年修订版）的危险分层标准,分为3个组：Ⅰ组（中危组）、Ⅱ组（高危组）、Ⅲ组（极高危组）。分别检测其外周血HCY水平并进行组间比较。结果随着危险程度的增高,血HCY的浓度也逐渐升高,而极高危的患者则明显的升高,Ⅰ组与Ⅲ组、Ⅱ组与Ⅲ组HCY水平间差异均有统计学意义（P〈0．05）。血HCY浓度与高血压的危险程度呈正相关。结论高血压患者血HCY值与高血压患者的危险等级密切相关,血HCY值有助于判断高血压患者发生心、脑、血管意外的危险性及脏器受伤的程度,对高血压的预防、诊断和治疗具有一定的临床指导意义。     

泽泻对肝硬化门脉高压大鼠血流动力学的影响

目的研究泽泻对肝硬化门脉高压血流动力学的影响,寻求治疗肝硬化门脉高压的理想药物.方法采用40%四氯化碳诱导大鼠肝硬化门脉高压模型.对肝硬化门脉高压大鼠进行泽泻灌胃治疗(每日5 g/kg,疗程1个月),然后测定尿量、门静脉压力、肠系膜上动脉血流量和血管阻力、平均动脉压等血流动力学指标.应用放射免疫法测定泽泻治疗前后血浆肾素和醛固酮水平.以中药丹参作为治疗对照组.结果泽泻具有明显利尿作用,治疗后可使肝硬化大鼠尿量明显增加[(12.33士5.55)(31.05±24.91)ml/24 h,P＜O.01)],并能够显著减少肠系膜上动脉血流量[(34.39士12.20)(21.96士4.16)ml/(min·kg),P＜0.01)]和门静脉压力[(1.90士O.21)(1.44士O.33)kPa,P＜O.05)].泽泻治疗前后血浆肾素、醛固酮水平无明显改变.结论泽泻具有明显降低肝硬化门脉压力的作用,可能是通过利尿和减少肠系膜上动脉血流量发挥作用.泽泻可作为治疗肝硬化门脉高压的有效药物.