Hepatocellular Telomere Length in Biliary Atresia Measured by Q-FISH
Hepatocellular Telomere Length in Biliary Atresia Measured by Q-FISH
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DOI：
10.1007/s00268-012-1453-z
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发表时间：
2012-04-01
影响因子：
2.6
通讯作者：
Takubo, Kaiyo
中科院分区：
文献类型：
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作者：
Sanada, Yukihiro;Aida, Junko;Takubo, Kaiyo
当加塞门肠吻合术被认为不可行时，肝移植治疗胆道闭锁是有指征的。然而，胆道闭锁的肝移植时机尚未确切确定。肝细胞端粒的过度缩短可能发生在胆道闭锁的患者，因此，端粒长度可能是肝细胞储备capacity.肝组织的预测从20例胆道闭锁谁接受LT和10个年龄匹配的尸检个人（平均年龄，1.7和1.2岁，分别）。端粒长度通过Southern印迹和定量荧光原位杂交使用标准化的端粒-着丝粒比率测量。分析胆道闭锁组肝细胞端粒-着丝粒比值与儿童终末期肝病评分的相关性，胆道闭锁组肝组织末端限制性片段长度中位数与对照组比较无显著性差异（p = 0.425），而胆道闭锁组肝细胞端粒-着丝粒比值中位数明显小于对照组（p < 0.001）。回归分析显示，正常化端粒-着丝粒比值与胆道闭锁患儿终末期肝病评分呈负相关（p < 0.001），应用荧光原位杂交技术进行端粒长度分析可作为胆道闭锁患者肝细胞储备能力的客观指标，而过度的端粒缩短支持肝移植的早期实施。
Liver transplantation for biliary atresia is indicated whenever a Kasai portoenterostomy is considered unfeasible. However, the timing of liver transplantation in biliary atresia has not been precisely defined. Excessive shortening of hepatocellular telomeres may occur in patients with biliary atresia, and therefore, telomere length could be a predictor of hepatocellular reserve capacity.Hepatic tissues were obtained from 20 patients with biliary atresia who underwent LT and 10 age-matched autopsied individuals (mean age, 1.7 and 1.2 years, respectively). Telomere lengths were measured by Southern blotting and quantitative fluorescence in situ hybridization using the normalized telomere-centromere ratio. The correlation between the normalized telomere-centromere ratio for the hepatocytes in biliary atresia and the pediatric end-stage liver disease score was analyzed.The median terminal restriction fragment length of the hepatic tissues in biliary atresia was not significantly different from that of the control (p = 0.425), whereas the median normalized telomere-centromere ratio of hepatocytes in biliary atresia was significantly smaller than that of the control (p < 0.001). Regression analysis demonstrated a negative correlation of the normalized telomere-centromere ratio with the pediatric end-stage liver disease score in biliary atresia (p < 0.001).Telomere length analysis using quantitative fluorescence in situ hybridization could be an objective indicator of hepatocellular reserve capacity in patients with biliary atresia, and excessive telomere shortening supports the early implementation of liver transplantation.