An electron microscopic and morphometric study of ursodeoxycholic effect in primary biliary cirrhosis
An electron microscopic and morphometric study of ursodeoxycholic effect in primary biliary cirrhosis
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DOI：
10.1046/j.0106-9543.2002.01640.x
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发表时间：
2002-06-01
期刊：
影响因子：
--
通讯作者：
Blendis, LM
中科院分区：
文献类型：
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作者：
Neuman, MG;Cameron, RG;Blendis, LM
背景/目的：原发性胆汁性肝硬化（PBC）是一种导致胆汁淤积和胆管丢失的慢性肝病。熊去氧胆酸（UDCA）已被证明可以减少PBC的肝细胞损伤。该研究试图量化随机对照试验中接受UDCA治疗的患者与接受安慰剂治疗的患者PBC肝活检中窦周胶原化和凋亡小体的数量。研究方法：将28例PBC患者（10例胆汁性，18例非胆汁性; 13例接受UDCA治疗，15例接受安慰剂治疗）与32例光学显微镜下肝组织学正常的对照组进行比较。使用电子显微镜检查肝活检的窦周纤维化程度和细胞凋亡活性。结果：UDCA和安慰剂治疗患者的预处理活检中窦周纤维化程度和凋亡活性相似。服用安慰剂两年后，患者的纤维化程度显著增加（P < 0.001）。相比之下，在接受UDCA治疗的动脉粥样硬化患者中，非动脉粥样硬化无变化，纤维化减少。在基线时，PBC患者的凋亡细胞数量（凋亡细胞/100个肝细胞+/- SE）（7 +/- 3）高于对照组（2 +/- 0.5）（P < 0.05），两组患者中的肝硬化和非肝硬化患者之间没有差异。两年后，UDCA治疗患者的凋亡细胞数量与基线相比显著减少（3 +/-2）（P < 0.05）;安慰剂组患者的凋亡细胞数量增加（12 +/-5）（P < 0.05）。结论：UDCA治疗2年后可防止PBC患者窦周胶原沉积，并降低细胞凋亡活性。
Background/aims: Primary biliary cirrhosis (PBC) is a chronic liver disease that results in cholestasis and bile duct loss. Ursodeoxycholic acid (UDCA) has been shown to reduce hepatocellular damage in PBC. The study attempted to quantify perisinusoidal collagenization and the number of apoptotic bodies in PBC liver biopsies from patients in a randomized control trial treated with UDCA compared to those who received placebo. Methods: Twenty-eight patients with PBC (10 cirrhotic, 18 non-cirrhotic; 13 treated with UDCA, 15 treated with placebo) were compared with 32 controls with normal hepatic histology on light mictoscopy. Liver biopsies were examined for degree of perisinusoidal fibrosis and apoptotic activity using electron microscopy. Results: The degree of perisinusoidal fibrosis and apoptotic activity was similar in pretreatment biopsies of UDCA and placebo-treated patients. After two years of placebo, patients showed a significant increase in fibrosis (P < 0.001). In contrast, there were no changes in non-cirrhotic and a decrease in fibrosis in cirrhotic patients given UDCA. At baseline, PBC patients had higher numbers (apoptotic cells/100 hepatocytes +/- SE) of apoptotic cells (7 +/- 3), than controls (2 +/- 0.5) (P < 0.05), with no difference between cirrhotic and non-cirrhotic patients in the two groups of patients. After two years, the numbers of apoptotic cells in UDCA-treated patients decreased significantly compared to baseline (3 +/-2) (P < 0.05); with placebo patients the number of apoptotic cells increased (12 +/- 5) (P < 0.05). Conclusion: Treatment with UDCA prevents the deposition of perisinusoidal collagen and reduces the apoptotic activity in PBC patients after 2 years of therapy.