目的:探讨熊去氧胆酸、腺苷蛋氨酸联合多烯磷脂酰胆碱对妊娠期肝内胆汁淤积症(ICP)患者相关指标的影响。方法:回顾性分析90例ICP患者资料,按用药的不同分为对照组(45例)和观察组(45例)。对照组患者给予熊去氧胆酸片300 mg,口服,每日3次...目的:探讨熊去氧胆酸、腺苷蛋氨酸联合多烯磷脂酰胆碱对妊娠期肝内胆汁淤积症(ICP)患者相关指标的影响。方法:回顾性分析90例ICP患者资料,按用药的不同分为对照组(45例)和观察组(45例)。对照组患者给予熊去氧胆酸片300 mg,口服,每日3次+注射用丁二磺酸腺苷蛋氨酸1 g,加入5%葡萄糖注射液250 m L中,静脉滴注,每日1次。观察组患者在对照组治疗的基础上给予多烯磷脂酰胆碱注射液15 m L,加入5%葡萄糖注射液250 m L中,静脉滴注,每日1次。两组疗程均为2周。观察两组患者治疗前后瘙痒评分、血清胆汁酸(TBA)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平,妊娠结局及不良反应发生情况。结果:治疗前,两组患者瘙痒评分和TBA、ALT、AST水平比较,差异均无统计学意义(P>0.05)。治疗后,两组患者瘙痒评分和TBA、ALT、AST水平均显著低于同组治疗前,且观察组显著低于对照组,差异均有统计学意义(P<0.05)。观察组患者剖宫产、早产、胎儿窘迫和羊水粪染发生率均显著低于对照组,差异均有统计学意义(P<0.05)。两组患者治疗期间均未见明显不良反应发生。结论:熊去氧胆酸、腺苷蛋氨酸联合多烯磷脂酰胆碱可有效改善ICP患者的瘙痒症状、肝功能及妊娠结局,且安全性较好。展开更多
Several studies have characterized the cellular and molecular mechanisms of hepatocyte injury caused by the retention of hydrophobic bile acids （BAs） in cholestatic diseases. BAs may disrupt cell membranes through t...Several studies have characterized the cellular and molecular mechanisms of hepatocyte injury caused by the retention of hydrophobic bile acids （BAs） in cholestatic diseases. BAs may disrupt cell membranes through their detergent action on lipid components and can promote the generation of reactive oxygen species that, in turn, oxidatively modify lipids, proteins, and nucleic acids, and eventually cause hepatocyte necrosis and apoptosis. Several pathways are involved in triggering hepatocyte apoptosis. Toxic BAs can activate hepatocyte death receptors directly and induce oxidative damage, thereby causing mitochondrial dysfunction, and induce endoplasmic reticulum stress. When these compounds are taken up and accumulate inside biliary cells, they can also cause apoptosis. Regarding extrahepatic tissues, the accumulation of BAs in the systemic circulation may contribute to endothelial injury in the kidney and lungs. In gastrointestinal cells, BAs may behave as cancer promoters through an indirect mechanism involving oxidative stress and DNA damage, as well as acting as selection agents for apoptosis-resistant cells. The accumulation of BAs may have also deleterious effects on placental and fetal cells. However, other BAs, such as ursodeoxycholic acid, have been shown to modulate BA-induced injury in hepatocytes. The major beneficial effects of treatment with ursodeoxycholic acid are protection against cytotoxicity due to more toxic BAs; the stimulation of hepatobiliary secretion; antioxidant activity, due in part to an enhancement in glutathione levels; and the inhibition of liver cell apoptosis. Other natural BAs or their derivatives, such as cholyI-N- methylglycine or pharmacological properties. cholylsarcosine, interest owing have also aroused to their protective展开更多
妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)是妊娠期妇女特有的严重并发症之一,临床上以皮肤瘙痒和血清胆汁酸升高(>10μmol/L)为主要特征,重症可伴有黄疸和肝酶升高,常发生于妊娠中晚期。分娩后ICP的临床症...妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)是妊娠期妇女特有的严重并发症之一,临床上以皮肤瘙痒和血清胆汁酸升高(>10μmol/L)为主要特征,重症可伴有黄疸和肝酶升高,常发生于妊娠中晚期。分娩后ICP的临床症状和实验室异常指标常可自动恢复正常,对孕妇危害不大,主要在孕期危及胎儿,容易引发胎儿宫内缺氧、羊水污染、早产、新生儿呼吸窘迫等并发症,严重者可造成胎死宫内或死产[1]。ICP病因十分复杂,目前发病机制尚不明确,可能与遗传、雌激素水平及环境等因素相关。产前检查时对ICP高危孕妇筛查肝功能和血清胆汁酸水平,有利于ICP的早期发现和诊治。展开更多
文摘目的:探讨熊去氧胆酸、腺苷蛋氨酸联合多烯磷脂酰胆碱对妊娠期肝内胆汁淤积症(ICP)患者相关指标的影响。方法:回顾性分析90例ICP患者资料,按用药的不同分为对照组(45例)和观察组(45例)。对照组患者给予熊去氧胆酸片300 mg,口服,每日3次+注射用丁二磺酸腺苷蛋氨酸1 g,加入5%葡萄糖注射液250 m L中,静脉滴注,每日1次。观察组患者在对照组治疗的基础上给予多烯磷脂酰胆碱注射液15 m L,加入5%葡萄糖注射液250 m L中,静脉滴注,每日1次。两组疗程均为2周。观察两组患者治疗前后瘙痒评分、血清胆汁酸(TBA)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平,妊娠结局及不良反应发生情况。结果:治疗前,两组患者瘙痒评分和TBA、ALT、AST水平比较,差异均无统计学意义(P>0.05)。治疗后,两组患者瘙痒评分和TBA、ALT、AST水平均显著低于同组治疗前,且观察组显著低于对照组,差异均有统计学意义(P<0.05)。观察组患者剖宫产、早产、胎儿窘迫和羊水粪染发生率均显著低于对照组,差异均有统计学意义(P<0.05)。两组患者治疗期间均未见明显不良反应发生。结论:熊去氧胆酸、腺苷蛋氨酸联合多烯磷脂酰胆碱可有效改善ICP患者的瘙痒症状、肝功能及妊娠结局,且安全性较好。
基金Supported by Instituto de Salud CarlosTM,FIS, Spain (GrantsPI070517 and PI080151)Fundacion Investigacion Medica Mutua Madrilea, Spain (Conv-TM,, 2006)+3 种基金Junta de Castillay Leon, Spain (Grants GR75-2008, SA033A08, SA03508 and SA03608)Ministerio de Ciencia y Tecnologia, Plan Nacional de Investigacion Cientifi ca, Desarrollo e Innovacion Tecnologica, Spain (Grant BFU2006-12577)The group is member of the Network for Cooperative Research on Membrane Transport Proteins (REIT), co-funded by the Ministerio de Educacion y Ciencia, Spain, and the European Regional Development Fund (ERDF) (Grant BFU2007-30688-E/BFI)belongs to the CIBERehd (Centro de Investigacion Biomedica en Red para el Estudio de Enfermedades Hepaticas y Digestivas), Instituto de Salud CarlosTM
文摘Several studies have characterized the cellular and molecular mechanisms of hepatocyte injury caused by the retention of hydrophobic bile acids （BAs） in cholestatic diseases. BAs may disrupt cell membranes through their detergent action on lipid components and can promote the generation of reactive oxygen species that, in turn, oxidatively modify lipids, proteins, and nucleic acids, and eventually cause hepatocyte necrosis and apoptosis. Several pathways are involved in triggering hepatocyte apoptosis. Toxic BAs can activate hepatocyte death receptors directly and induce oxidative damage, thereby causing mitochondrial dysfunction, and induce endoplasmic reticulum stress. When these compounds are taken up and accumulate inside biliary cells, they can also cause apoptosis. Regarding extrahepatic tissues, the accumulation of BAs in the systemic circulation may contribute to endothelial injury in the kidney and lungs. In gastrointestinal cells, BAs may behave as cancer promoters through an indirect mechanism involving oxidative stress and DNA damage, as well as acting as selection agents for apoptosis-resistant cells. The accumulation of BAs may have also deleterious effects on placental and fetal cells. However, other BAs, such as ursodeoxycholic acid, have been shown to modulate BA-induced injury in hepatocytes. The major beneficial effects of treatment with ursodeoxycholic acid are protection against cytotoxicity due to more toxic BAs; the stimulation of hepatobiliary secretion; antioxidant activity, due in part to an enhancement in glutathione levels; and the inhibition of liver cell apoptosis. Other natural BAs or their derivatives, such as cholyI-N- methylglycine or pharmacological properties. cholylsarcosine, interest owing have also aroused to their protective
文摘妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)是妊娠期妇女特有的严重并发症之一,临床上以皮肤瘙痒和血清胆汁酸升高(>10μmol/L)为主要特征,重症可伴有黄疸和肝酶升高,常发生于妊娠中晚期。分娩后ICP的临床症状和实验室异常指标常可自动恢复正常,对孕妇危害不大,主要在孕期危及胎儿,容易引发胎儿宫内缺氧、羊水污染、早产、新生儿呼吸窘迫等并发症,严重者可造成胎死宫内或死产[1]。ICP病因十分复杂,目前发病机制尚不明确,可能与遗传、雌激素水平及环境等因素相关。产前检查时对ICP高危孕妇筛查肝功能和血清胆汁酸水平,有利于ICP的早期发现和诊治。
