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浙江大学学报（医学版） 2012年第3期41卷 339-344页

作者：陈炳权周燕丰浙江大学医学院附属第一医院麻醉科浙江杭州310003

肝硬化与胰岛素抵抗密切相关,临床表现为高糖血症、高胰岛素血症、高脂血症以及各种细胞因子的异常增高,其病理机制目前尚不明确。近来研究发现,肝硬化胰岛素抵抗与胰岛素受体底物有关,而胰岛素受体底物是胰岛素信号传导通路中的关键信... 详细信息

肝硬化与胰岛素抵抗密切相关,临床表现为高糖血症、高胰岛素血症、高脂血症以及各种细胞因子的异常增高,其病理机制目前尚不明确。近来研究发现,肝硬化胰岛素抵抗与胰岛素受体底物有关,而胰岛素受体底物是胰岛素信号传导通路中的关键信号分子,它可通过表达上调或下调、翻译后修饰,以及亚细胞定位来改变胰岛素信号的传导,其中翻译后修饰中的磷酸化/去磷酸化显得尤为重要且较为复杂。再者,不同病因的肝硬化胰岛素受体底物的作用途径并不相同。

关键词：肝硬化/病理生理学胰岛素抗药性受体,胰岛素/代谢糖尿病

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阿德福韦治疗YMDD变异失代偿肝硬化13例的临床观察

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浙江大学学报（医学版） 2005年第5期34卷 470-472页

作者：苏关关赵年丰周勇应美芳浙江大学医学院附属邵逸夫医院浙江杭州310016 浙江大学医学院附属第一医院浙江杭州310003 华东医药股份有限公司浙江杭州310009

目的:观察阿德福韦治疗在接受拉米夫定治疗过程中出现YMDD变异失代偿肝硬化的疗效和安全性。方法:14例慢性乙型病毒性肝炎失代偿性肝硬化患者,在接受拉米夫定治疗过程中取得明显疗效后,因乙肝病毒产生YMDD变异,出现HBVDNA复阳,肝炎活动... 详细信息

目的:观察阿德福韦治疗在接受拉米夫定治疗过程中出现YMDD变异失代偿肝硬化的疗效和安全性。方法:14例慢性乙型病毒性肝炎失代偿性肝硬化患者,在接受拉米夫定治疗过程中取得明显疗效后,因乙肝病毒产生YMDD变异,出现HBVDNA复阳,肝炎活动,肝功能失代偿,经评估14例均为CPS-C级。采用拉米夫定减量(50mg/d)与阿德福韦10mg/d联合治疗6个月。结果:除1例因出现非缺氧性高乳酸血症中途退出,13例治疗半年显示HBVDNA的拷贝数降至≤105copei/ml、≤104copei/ml的比例分别为100%、53.85%。ALT复常达46.15%,Child-Pugh积分下降。结论:阿德福韦治疗在接受拉米夫定用药过程中出现YMDD变异失代偿肝硬化的患者中表现出良好的疗效和安全性。

关键词：肝炎病毒乙型/药物作用核苷类抗病毒药拉米夫定/治疗应用阿德福韦/治疗应用变异(遗传学) 肝硬化/药物疗法肝硬化/病理生理学

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肝硬化患者血浆前列环素、肿瘤坏死因子与门脉高压的关系

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陕西医学杂志 2006年第3期35卷 307-309页

作者：罗亚文李佳易学东遵义医学院附属医院遵义563003

目的探讨前列环素(PGI2)及肿瘤坏死因子(TNF)在乙肝后肝硬化门脉高压形成中的作用。方法电子胃镜了解有无食管胃底静脉曲张,B超探测门静脉内径,放免法检测血浆6-K-PGF1a及TNF水平。结果肝硬化食管胃底静脉曲张组患者门静脉内径增宽明显... 详细信息

目的探讨前列环素(PGI2)及肿瘤坏死因子(TNF)在乙肝后肝硬化门脉高压形成中的作用。方法电子胃镜了解有无食管胃底静脉曲张,B超探测门静脉内径,放免法检测血浆6-K-PGF1a及TNF水平。结果肝硬化食管胃底静脉曲张组患者门静脉内径增宽明显;肝硬化患者血浆6-K-PGF1a及TNF均升高,且食管胃底静脉曲张组升高更明显,其水平与门静脉内径呈显著正相关;肝硬化患者血浆6-K-PGF1a、TNF间呈正相关。结论PGI2及TNF间相互作用,共同参与了肝硬化时肝损伤及门脉高压的形成。

关键词：肝硬化/病理生理学前列腺素/分析肿瘤坏死因子/分析门静脉压

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彩色多普勒超声监测肝硬化门脉系统血流动力学与一氧化氮关系的研究

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陕西医学杂志 2006年第7期35卷 779-781页

作者：张爱芸刘娅袁迎春赵经川宁夏医学院附属医院感染疾病科银川750004

目的:采用彩色多普勒超声检测门静脉血流动力学指标并测定一氧化氮(NO)在肝硬化不同肝功能状态下的血清表达,以探讨其二者在肝硬化门脉高压诊断中的应用价值。方法:应用彩色多普勒超声检测门静脉最大截面直径(PVD)及血流速度(PVV);采用... 详细信息

目的:采用彩色多普勒超声检测门静脉血流动力学指标并测定一氧化氮(NO)在肝硬化不同肝功能状态下的血清表达,以探讨其二者在肝硬化门脉高压诊断中的应用价值。方法:应用彩色多普勒超声检测门静脉最大截面直径(PVD)及血流速度(PVV);采用硝酸还原酶法测定血清NO浓度。结果:肝硬化患者血清NO水平均显著高于对照组。按照肝功能Ch ild-Pugh分级,各组血清NO水平依次升高。肝硬化患者PVD均显著高于对照组、PVV显著低于对照组,按照肝功能Ch ild-Pugh分级,其中C组内径显著大于A组及B组、PVV显著低于A组及B组,PVD和PVV在A组和B组之间无显著性差异。血清NO水平与PVD呈正相关;与PVV呈负相关。结论:肝硬化患者存在内脏高动力循环和门静脉高阻力状态。NO影响肝硬化患者门静脉血流动力学,彩色多普勒超声及血清NO水平在门脉高压症的诊断中有一定的应用价值。

关键词：肝硬化/病理生理学一氧化氮/分析血液动力学超声检查多普勒彩色

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结缔组织生长因子在大鼠肝纤维化发生中的作用机制初探

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陕西医学杂志 2006年第11期35卷 1411-1413,1418页

作者：梁增文张国农兵广西壮族自治区人民医院消化内科南宁530021

目的：研究结缔组织生长因子（CTGF）在大鼠肝纤维化形成中的作用机制。方法：雄性SD大鼠32只，体重250～300g，皮下注射四氯化碳（CCl4）制备大鼠肝纤维化模型，分别于注射后1、4、8周处理动物，采用免疫组化、RT-PCR、Western blot等... 详细信息

目的：研究结缔组织生长因子（CTGF）在大鼠肝纤维化形成中的作用机制。方法：雄性SD大鼠32只，体重250～300g，皮下注射四氯化碳（CCl4）制备大鼠肝纤维化模型，分别于注射后1、4、8周处理动物，采用免疫组化、RT-PCR、Western blot等方法对肝组织中CTGF的表达进行检测。结果：免疫组化、Western blot结果显示，CCl4注射诱导后，大鼠肝组织中CTGF的表达较正常对照明显增强，且CCl4注射1、4、8周组肝组织中CTGF的表达强度呈明显递增趋势。CTGF主要表达于肝星状细胞胞质中。RT-PCR检测结果显示CTGF mRNA的表达与其蛋白质水平的改变相一致。结论：CTGF作为一种致纤维化因子，其过表达促进肝星状细胞的活化增殖及细胞外基质的形成，从而促进大鼠肝纤维化的发生、发展。

关键词：肝硬化/病理生理学结缔组织生长因子/免疫学肝星状细胞大鼠

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Prevalence of hypoxemia in 102 Japanese patients with alcoholic and nonalcoholic cirrhosis

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AMERICAN JOURNAL OF GASTROENTEROLOGY 1999年第10期94卷 2994-2999页

作者： Maruyama, S Hirayama, C Oyake, N Kadowaki, Y Umeki, K Sagayama, A Kato, K Fukuda, K Kuzuo, H Ohuchi, Y Saiseikai Gotsu Gen Hosp Dept Internal Med Gotsu Shimane 695 Japan Saiseikai Gotsu Gen Hosp Dept Radiol Gotsu Shimane 695 Japan

OBJECTIVE: Liver cirrhosis is often accompanied by arterial hypoxemia in the absence of cardiopulmonary disease. The aim of this study was to investigate the relationship between various clinicopathological conditions and the hypoxemia seen in Japanese patients with liver cirrhosis. METHODS: In 102 consecutive patients with alcoholic (N = 45) and nonalcoholic (N = 57 cirrhosis not associated with cardiopulmonary disease, we performed lung perfusion scintigraphy, contrast echocardiography, and arterial blood gas analysis and measured oxygen consumption. RESULTS: No abnormality was seen in pulmonary blood flow in cirrhotic patients, but 38 (38%) of them had a decreased partial pressure of oxygen (PaO2). The hypoxemic patients did not show any pulmonary signs or symptoms. The hypoxemia was not: associated with the Child-Pugh grade, and was observed in 32 (71%) of the 45 alcoholic patients but in only six (11%) of the 57 nonalcoholic patients (p < 0.001). Oxygen consumption was sig nificantly higher in the alcoholic group than in the nonalcoholic group (p < 0.0001), and a high incidence of oxygen consumption was seen in all 45 (100%) of the alcoholic patients and in 34 (60%) of the nonalcoholic subjects, the difference being significant (p < 0.01). The relationship between oxygen consumption and PaO2 in the 102 cirrhotic patients showed an inverse correlation (r = -0.85, p < 0.0001). Among the alcoholic patients, the incidence of hypoxemia did not differ between the 33 smokers and the 22 nonsmokers. After 1 wk of abstinence from alcohol a significant increase (p < 0.0001) in the PaO2 was seen in 14 of 19 patients with alcoholic cirrhosis. CONCLUSIONS: We conclude that the hypoxemia in Japanese patients with liver cirrhosis occurs mainly in drinking alcoholic patients, presumably due to an increased oxygen consumption by alcohol. (C) 1999 by Am. Coll. of Gastroenterology.

关键词：超声心动描记术日本肝硬化/并发症肝硬化/病理生理学肝硬化酒精性/并发症肝硬化酒精性/病理生理学肺/放射性核素显像氧/血液氧耗量肺循环老年人老年人 80以上女(雌)性人类男(雄)性中年人

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Role of substance P in the pathogenesis of spider angiomas in patients with nonalcoholic liver cirrhosis

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AMERICAN JOURNAL OF GASTROENTEROLOGY 1999年第2期94卷 502-507页

作者： Li, CP Lee, FY Hwang, SJ Chang, FY Lin, HC Lu, RH Hou, MC Chu, CJ Chan, CC Luo, JC Lee, SD Vet Gen Hosp Dept Med Div Gastroenterol Taipei 11217 Taiwan Natl Yang Ming Univ Sch Med Taipei 112 Taiwan

Objective: Cutaneous spider angioma is a common sign observed in patients with liver cirrhosis, but its pathogenesis is still unclear. Increased plasma levels of estrogen, vascular dilation, and neovascularization are possible etiologies. This study was designed to investigate the relationship of spider angiomas in patients with nonalcoholic liver cirrhosis to the plasma levels of sex hormones and various vasodilators and hemodynamic parameters. Methods: A total of 60 patients with nonalcoholic liver cirrhosis and 20 healthy subjects were included in this study. The number, size, and location of the spider angiomas were recorded. Plasma levels of estradiol, testosterone, substance P, calcitonin gene-related peptide, and nitrate/nitrite and forearm hemodynamics were measured. Results: Cirrhotic patients showed higher plasma estradiol/testosterone ratios (28.3 +/- 47.2 x 10(-3), median 10.5 x 10(-3) vs 8.2 +/- 8.3 x 10(-3), median 5.7 x 10(-3), p = 0.003) and levels of nitrate/nitrite (29.9 +/- 17.5, median 23.8 vs 21.4 +/- 10.0, median 20.6 mu mol/L, p = 0.01) and substance P (47.5 +/- 62.5, median 29.2 vs 15.2 +/- 7.7, median 12.3 pg/ml, p < 0.001) than healthy controls. Sixteen (27%) of the 60 cirrhotic patients had spider angiomas. Cirrhotic patients with spider angiomas disclosed higher plasma levels of substance P (84.7 +/- 105.3, median 53.1 vs 34.5 +/- 30.7, median 25.8 pg/ml, p = 0.006) and serum levels of bilirubin (3.9 +/- 3.8, median 1.9 vs 1.9 +/- 1.9, median 1.2 mg/dl, p = 0.02) than those without. Stepwise logistic regression showed substance P was the only significant and independent predictor associated with the presence of spider angiomas in cirrhotic patients (odds ratio 3.0, 95% confidence interval = 1.4-6.6, p = 0.01). Conclusion: Plasma levels of substance P are elevated in patients with nonalcoholic cirrhosis and may play an important role in the pathogenesis of spider angiomas. (Am J Gastroenterol 1999;94:502-507. (C) 1999 by Am. Coll. of Gastr

关键词：病例对照研究雌二醇/血液前臂/血液供给肝硬化/血液肝硬化/并发症肝硬化/病理生理学 Logistic模型局部血流/生理学 P物质/血液 P物质/生理学毛细血管扩张/病因学睾酮/血液血管舒张药/血液老年人女(雌)性人类男(雄)性

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Rheologic analysis of gastric mucosal hemodynamics in patients with cirrhosis

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GASTROINTESTINAL ENDOSCOPY 1999年第3期49卷 371-379页

作者： Masuko, E Homma, H Ohta, H Nojiri, S Koyama, R Niitsu, Y Sapporo Med Univ Dept Internal Med 4 Sch Med Chuo Ku Sapporo Hokkaido 060 Japan Shinnittetsu Muroran Gen Hosp Dept Gastroenterol Muroran Hokkaido Japan Hokkaido Kitano Hosp Dept Internal Med Muroran Hokkaido Japan

Background: Portal hypertensive gastropathy causes some gastric mucosal microcirculatory disorders in cirrhotic patients, but the nature of the theologic dysfunction in the gastric microcirculation remains to be clarified. Methods: To examine the rheologic properties of the gastric microcirculation, we subjected 112 cirrhotic patients and 51 control subjects to endoscopic laser Doppler flowmetry and measured multiple variables of flow, red blood cell volume, and velocity. Furthermore, based on these results, we analyzed the shear rate which reflects the status of the microcirculatory system. To validate the laser Doppler flowmetry, we derived the relationship between red blood cell volume and cross-sectional areas of submucosal collecting venules;near-infrared endoscopy was used to evaluate this relationship, Results: Analysis of shear rate according to the severity of portal hypertensive gastropathy showed that the mucosa was exposed to strong hemokinetic stress in severe cases, characterized by a higher shear rate than in control subjects or in mild cases. Nitroglycerin, administered by intravenous infusion (1.0 mu g/kg/min), reduced blood flow and restored shear rate to control levels in patients with severe portal hypertensive gastropathy. Conclusion: This theologic study of the gastric mucosa suggests that a disorder of the shear rate control mechanism in the microcirculation is associated with severe portal hypertensive gastropathy.

关键词：内窥镜检查消化系统红细胞容量胃黏膜/血液供给血流动力学/生理学激光多普勒流量测定肝硬化/病理生理学微循环/生理学硝酸甘油/药理学流变学女(雌)性人类男(雄)性中年人

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ISOPROTERENOL IN OFFSETTING ADVERSE EFFECTS OF VASOPRESSIN IN CIRRHOTIC PATIENTS

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AMERICAN JOURNAL OF SURGERY 1975年第2期129卷 130-136页

作者： SIRINEK, KR THOMFORD, NR OHIO STATE UNIV COLL MEDDEPT SURGCOLUMBUSOH 43210

Vasopressin administered as a peripheral infusion (40 U/hr) significantly reduced portal vein pressure in ten awake patients with cirrhosis and portal hypertension. A vasopressin-induced reduction in cardiac output occurred in five of the ten patients (50 per cent). Vasopressin-induced changes in systemic arterial pressure, heart rate, and portal venous pressure were independent of alterations in cardiac output. When the five patients with vasopressin-induced reductions in cardiac output were given a combination of vasopressin and isoproterenol, cardiac output was maintained and the reduction in portal vein pressure was equal to that observed with unopposed vasopressin therapy. Thus, the addition of isoproterenol prevented a vasopressin-induced reduction in cardiac output while permitting vasopressin to reduce portal vein pressure.

关键词：血压/药物作用心排血量/药物作用药物评价食管和胃静脉曲张/药物疗法胃肠出血/药物疗法心率/药物作用输注胃肠外异丙肾上腺素/治疗应用肝硬化/并发症肝硬化/病理生理学门脉系统/药物作用血管升压素类/投药和剂量血管升压素类/治疗应用女(雌)性人类男(雄)性

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Proton magnetic resonance spectroscopy (¹H-MRS) findings for the brain in patients with liver cirrhosis reflect the hepatic functional reserve

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AMERICAN JOURNAL OF GASTROENTEROLOGY 1999年第8期94卷 2206-2213页

作者： Lee, JH Seo, DW Lee, YS Kim, ST Mun, CW Lim, TH Min, YI Suh, DJ Univ Ulsan Coll Med Asan Med Ctr Div GastroenterolDept Internal Med Seoul 138736 South Korea Univ Ulsan Coll Med Asan Med Ctr Dept Radiol Seoul South Korea Univ Ulsan Coll Med Asan Inst Life Sci NMR Lab Seoul South Korea

OBJECTIVE: Proton magnetic resonance spectroscopy (H-1-MRS) has been used to assess the metabolic changes in the brain in patients with liver cirrhosis. Decreased myo-inositol and increased glutamine levels were noted to be the most sensitive spectroscopic markers for cirrhotic patients with hepatic encephalopathy (HE). The purpose of this study was to assess how the abnormalities seen on the H-1-MRS of the brain in patients with liver cirrhosis are related to clinical and laboratory parameters. METHODS: In a prospective study, localized H-1-MRS was performed in the basal ganglia and parietal white matter regions in liver cirrhosis patients with (n = 48) and without (n = 52) HE and chronic hepatitis (CH) (n = 15), and in normal controls (n = 20). RESULTS: Among cirrhotic patients, the myo-inositol levels were significantly lower (p < 0.01) and the glutamine levels were higher (p < 0.05) for patients with HE than for those without HE. The myo-inositol and glutamine levels, respectively, were inversely (r = -0.50;p < 0.001) and linearly (r = 0.50;p < 0.001) related to the Child-Pugh score. However, by subgroup analysis of Child-Pugh class C patients, there were no significant differences in the myoinositol and glutamine levels between cirrhotic patients with (n = 40) and without HE (n = 24). A follow-up study of eight cirrhotic patients with HE showed no significant differences in the myo-inositol and glutamine levels after clinical improvement of HE. CONCLUSIONS: The abnormalities seen on the H-1-MRS of the brain of patients with liver cirrhosis are not Likely to reflect the severity of HE or acute alteration in the level of consciousness. Rather, we believe they represent the chronic metabolic derangement of the brain associated with hepatic functional reserve. (Am J Gastroenterol 1999;94:2206-2213. (C) 1999 by Am. Cell. of Gastroenterology).

关键词：天冬氨酸/类似物和衍生物天冬氨酸/代谢基底神经节/病理生理学脑/病理生理学胆碱/代谢肌酸酐/代谢能量代谢/生理学谷氨酰胺/代谢肝性脑病/病理生理学肌醇/代谢肝硬化/病理生理学肝功能试验磁共振波谱学顶叶/病理生理学预后前瞻性研究成年人老年人女(雌)性人类男(雄)性中年人

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