Ursodeoxycholic acid reduces expression of heat shock proteins in primary biliary cirrhosis.

Ursodeoxycholic acid reduces expression of heat shock proteins in primary biliary cirrhosis.
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熊去氧胆酸可降低原发性胆汁性肝硬化中热休克蛋白的表达。

DOI：
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发表时间：
2000
期刊：
Liver
影响因子：
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通讯作者：
K. Tanikawa
K. Tanikawa
中科院分区：
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文献类型：
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作者：
S. Sakisaka;H. Koga;K. Sasatomi;M. Ohishi;T. Kawaguchi;M. Harada;E. Taniguchi;Y. Uchimura;T. Ueno;M. Sata;K. Tanikawa

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背景 为了鉴定原发性胆汁性肝硬化（PBC）患者肝脏中受损的细胞，并确定熊去氧胆酸（UDCA）对这些细胞的影响，我们检测了UDCA治疗前后PBC中热休克蛋白（HSP）的细胞表达。 方法 采用免疫印迹法和免疫组化法检测34例PBC患者肝组织中HSP70和泛素的表达，并与9例慢性丙型肝炎、8例原发性硬化性胆管炎和7例对照组进行比较。 结果 免疫印迹分析显示PBC中HSP 70和ubiquitin的表达显著。免疫组化染色的HSP 70和泛素被观察到在胆管上皮细胞（BECs）和中度肝细胞和动脉PBC中的强。PBC患者胆管组织中HSP 70和泛素的细胞标记率显著高于慢性丙型肝炎、原发性硬化性胆管炎和对照组（P<0.01）。UDCA治疗后PBC胆管和肝细胞中HSP 70和泛素的标记率显著降低（p<0.01）。 结论 目前的数据表明，即使在PBC的早期阶段，BEC和肝细胞也显著表达HSP，UDCA治疗显著改善了它们的状况。HSPs的免疫组化检测是鉴别PBC损伤细胞的有效而敏感的方法。
BACKGROUND To identify injured cells in the liver of patients with primary biliary cirrhosis (PBC) and to determine the effects of ursodeoxycholic acid (UDCA) on these cells, we examined the cellular expression of heat shock proteins (HSPs) in PBC both before and after treatment with UDCA. METHODS Expression of HSP70 and ubiquitin in PBC livers (n=34) was evaluated immunohistochemically as well as by immunoblot analysis, and compared with chronic viral hepatitis type C (n= 9), primary sclerosing cholangitis (n=8), and controls (n=7). RESULTS Immunoblot analysis demonstrated a marked expression of HSP70 and ubiquitin in PBC. Immunohistochemical staining for both HSP70 and ubiquitin was observed to be strong in biliary epithelial cells (BECs) and moderate in both hepatocytes and arteries in PBC. Cellular labelling rates for HSP70 and ubiquitin of bile ducts in PBC were significantly higher (p<0.01) than those in chronic viral hepatitis type C, primary sclerosing cholangitis, or controls. The labelling rates for HSP70 and ubiquitin in bile ducts and in hepatocytes were significantly decreased (p<0.01) after treatment with UDCA in PBC. CONCLUSIONS The present data suggest that BECs and hepatocytes significantly express HSPs even in the early stages of PBC, and that UDCA treatment significantly improves their condition. The immunohistochemical evaluation of HSPs is a valid and sensitive means to identify injured cells in PBC.