Serum gamma glutamyl transferase as a specific indicator of bile duct lesions in the rat liver.
Serum gamma glutamyl transferase as a specific indicator of bile duct lesions in the rat liver.
复制标题
血清γ谷氨酰转移酶作为大鼠肝脏胆管病变的特异性指标。
作者：
T. Leonard;D. Neptun;J. Popp
血清γ-谷氨酰转移酶(GGT)是一种在人类中广泛使用的肝损伤标志物，但由于其特异性尚未确定，因此在大鼠身上很少使用。本研究旨在研究Fischer 344大鼠使用细胞类型特异性肝毒剂后血清GGT活性的特异性。单次致死剂量的CCl4、烯丙醇(AA)和α-异硫氰酸萘酯(ANIT)分别对小叶中心肝细胞、肝门周围肝细胞和胆管细胞造成细胞特异性损伤。CCl4可显著提高血清丙氨酸氨基转移酶(ALT)、碱性磷酸酶(AP)活性和血清胆汁酸浓度，但对血清GGT活性无明显影响。ANIT治疗后24小时血清GGT、AP活性和胆汁酸浓度均升高。烯丙醇可提高小鼠血清ALT活性，但对GGT活性无明显影响。在饲料中分别添加0.022%、0.022%、0.047%和0.1%的ANIT 2、4和6周后，血清GGT活性呈剂量和时间依赖性增加，这与肝脏胆管体积的数量增加密切相关，这是通过形态计量学测定的。这些观察结果支持将大鼠血清GGT活性作为胆管细胞坏死的诊断指标，在损伤后不久检测到升高，并作为可能的胆管增生的指标。
Serum gamma-glutamyl transferase (GGT), a marker of hepatic injury used extensively in humans, has been used rarely in rats because its specificity has not been previously defined. Studies were designed for investigation of the specificity of serum GGT activity with the use of cell type specific hepatotoxicants in Fischer 344 rats. Single necrogenic doses of CCl4, allyl alcohol (AA), and alpha-naphthylisothiocyanate (ANIT) were used to produce cell specific injury in centrilobular hepatocytes, periportal hepatocytes, and bile duct cells, respectively. Administration of CCl4 markedly increased serum activities of alanine aminotransferase (ALT), alkaline phosphatase (AP), and serum bile acid concentrations within 24 hours but had no effect on serum GGT activity. ANIT treatment increased serum GGT and AP activities and bile acid concentration 24 hours following administration. Allyl alcohol administration increased serum ALT activity but had no effect on GGT activity. Administration of ANIT in the diet at 0.01%, 0.022%, 0.047%, and 0.1% for 2, 4, and 6 weeks produced dose- and time-dependent increases in serum GGT activity which strongly correlated with quantitative increases in hepatic bile duct volume, which was determined morphometrically. These observations support the use of serum GGT activity in the rat as diagnostic of bile duct cell necrosis when increases are detected shortly after the insult and as an indicator of possible bile duct hyperplasia.