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表 1 熊去氧胆酸的作用机制主要作用 替代肠肝循环中的内源性 (疏水性 )胆盐 (竞争性抑制内源性胆盐的肠吸收 ) 竞争受体 (在毒性胆盐引起细胞损害的细胞器部位 )主要疗效 提高肝脏的排泌功能 细胞保护作用 ,阻止胆酸诱导的细胞溶解和凋亡 膜保护作用 ,防止胆酸诱导的膜损伤 (线粒体、基底膜和胆小管膜 ) 抗氧化作用 免疫调节作用继发疗效 减轻胆汁淤积 改善肝功能和组织形态改变 (一 )原发性胆汁性肝硬化 PBC是一种慢性胆汁淤积性疾病 ,中年妇女病人多见 ,以免疫介导的肝内小胆管损伤为特征。胆管的持续性损伤导致胆汁分泌障碍 ,引起疏水性毒性胆酸滞留并导致肝细胞损伤 ,所以 ,治疗PBC的关键是抑制异常的免疫反应 ,减轻郁积胆汁的毒性作用。在初始的无对照实验中 ,UDCA可改善症状 (主要是减轻瘙痒 )及有关胆汁淤积的生化指标 (胆红素、γ GT、碱性磷酸酶 ) ,并且减轻炎症。一个多中心对照实验证明 ,UDCA治疗组与安慰组比较 ,UDCA对高胆红素血症、腹水或消化道出血有显效。此后的几个对照研究证明生化指标有所改善 ,而仅有一项研究表明UDCA可改善病人症状 (疲乏和瘙痒不显著 )。UDCA对组织学的改善存在争议。有研究表明UDCA无组织学改善作用 ,而其他研究表明UDCA可改
Table 1 Ursodeoxycholic acid mechanism of action The main role of endogenous (hydrophobic) bile salts in the enterohepatic circulation (competitive inhibition of intestinal absorption of endogenous bile salts) competitive receptor (in toxic bile salts cause cells Damaged organelles site) Main effect Improve the excretory function of the liver Cell protection, prevent the bile acid-induced cell lysis and apoptosis Membrane protection, prevent bile acid-induced membrane damage (mitochondria, basement membrane and bile duct membrane) Oxidation Immunomodulatory effects Secondary efficacy Reduces cholestasis Ameliorates liver function and histological changes (1) Primary biliary cirrhosis PBC is a chronic cholestatic disease that is more common in middle-aged women and is immunologically mediated Small intrahepatic bile duct injury is characterized. Continuous bile duct injury lead to bile secretion disorders, causing hydrophobic toxic bile acid retention and lead to liver cell damage, therefore, the key to the treatment of PBC is to inhibit abnormal immune responses and reduce the toxic effects of deprivation bile. UDCA improves symptoms (mainly itching) and biochemical markers of cholestasis (bilirubin, γ GT, alkaline phosphatase) and reduces inflammation in initial, uncontrolled experiments. A multicenter controlled trial demonstrated that UDCA was markedly effective in patients with hyperbilirubinemia, ascites or gastrointestinal bleeding compared with placebo in the UDCA-treated group. Several subsequent controlled studies have shown biochemical markers to improve, and only one study showed that UDCA improved the patient’s symptoms (fatigue and itching are not significant). UDCA is controversial on the improvement of histology. Studies have shown that UDCA no histological improvement, while other studies show that UDCA can be changed