Efficacy of urine bile acid as a non-invasive indicator of liver damage in rats
Efficacy of urine bile acid as a non-invasive indicator of liver damage in rats
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DOI：
10.2131/jts.34.27
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发表时间：
2009-02-01
影响因子：
2
通讯作者：
Mitsumoto, Atsushi
中科院分区：
文献类型：
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作者：
Kawai, Hiroshi;Kudo, Naomi;Mitsumoto, Atsushi
肝损害评估在肝病的病理生理和毒理学研究中具有重要意义。作为一种新的、无创的肝损伤标志物，我们研究了尿胆汁酸（UBA）在大鼠肝脏疾病模型中的作用。本研究采用硫乙酰胺（TAA）处理大鼠。单次腹腔注射大剂量TAA可引起肝脏严重损伤，因此被用作急性肝炎模型。持续给予低剂量TAA会对肝脏产生轻微损害，并诱发肝硬化和肝肿瘤。在这项研究中，发现急性和慢性给药TAA都与UBA的剂量依赖性升高有关。UBA含量的升高与血液生化指标的改变相关，UBA筛选对肝损伤大鼠和健康大鼠具有显著的区分能力。特别是UBA分析对于筛选慢性肝损伤引起的血清碱性磷酸酶（ALP）活性异常的大鼠具有较高的敏感性、特异性和阳性的预测价值，经肝脏组织学分析证实包括胆汁淤积和随后的肝硬化。总之，我们证明测量UBA是一种简单、无创、有效的筛查taa治疗大鼠胆汁淤积的方法。我们认为，UBA分析可能在监测慢性肝病（如肝硬化和肝性脑病）动物模型的肝损伤进展方面具有强大的适用性。
Estimation of liver damage is important in the pathophysiological and toxicological study of liver disease. As a novel, non-invasive marker of liver damage, we studied the efficacy of urine bile acids (UBA) in a rat model of liver disease. Thioacetamide (TAA)-treated rats were used in this Study. Single intraperitoneal administration of high-dose TAA induces severe damage to the liver, and thus is used as a model of acute hepatitis. Continuous administration of low-dose TAA yields mild damage to the liver, and induces cirrhosis and hepatic tumors. In this study, it was found that both acute and chronic administration of TAA was associated with a dose-dependent elevation of UBA. The elevation of UBA content correlated with the alteration of blood biochemical indicators, and UBA screening showed a remarkable ability to distinguish liver-damaged rats from healthy rats. In particular, UBA analysis wits found to have high sensitivity, specificity, and positive predictive value for the screening of rats with abnormal serum alkaline phosphatase (ALP) activity due to chronic liver damage, which was confirmed to include cholestasis and subsequent cirrhosis by liver histological analysis. In conclusion, we demonstrated that measurement of UBA is a simple, non-invasive and effective method for the screening of cholestasis in TAA-treated rats. We suggest that UBA analysis may have potent applicability for monitoring the progress of liver damage in animal models of chronic liver disease, such as cirrhosis and hepatic encephalopathy.