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胃质子泵抑制剂雷贝拉唑对大鼠胆汁和肝脏溶酶体酶的影响。

Effects of rabeprazole, a gastric proton pump inhibitor, on biliary and hepatic lysosomal enzymes in rats.

作者信息

Fujisaki H, Oketani K, Nagakawa J, Takenaka O, Yamanishi Y

机构信息

Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.

出版信息

Jpn J Pharmacol. 1998 Mar;76(3):279-88. doi: 10.1254/jjp.76.279.

Abstract

The effects of rabeprazole (E3810), omeprazole and chloroquine on hepatic lysosomal function were studied. After chloroquine (50 mg/kg), rabeprazole (5 mg/kg) or omeprazole (5 mg/kg) was given intraperitoneally to rats for 6 days, the bile was collected via a bile duct cannula for 5 hr, and hepatic and biliary lysosomal enzyme (N-acetyl-beta-glucosaminidase and beta-galactosidase) activities were measured. The latency (an index for the hepatic lysosomal membrane integrity) was calculated from the N-acetyl-beta-glucosaminidase activity. The biliary constituents and plasma concentrations of lipids were also measured. The administration of chloroquine significantly increased hepatic and biliary lysosomal enzyme activities, but did not affect the lysosomal enzyme latency, hepatic and biliary protein content or bile flow. It significantly decreased the bile acid level. On the other hand, the administration of rabeprazole and omeprazole did not alter the lysosomal enzyme activities, lysosomal enzyme latency, protein content in liver or liver weight. Furthermore, no significant differences were observed in biliary lysosomal enzyme activity, protein content, bile flow, biliary constituents or in the plasma concentrations of lipids between the drug groups (rabeprazole or omeprazole) and the control group. The results of the present study indicate that rabeprazole, like omeprazole, does not influence hepatic lysosomal function.

摘要

研究了雷贝拉唑(E3810)、奥美拉唑和氯喹对肝脏溶酶体功能的影响。给大鼠腹腔注射氯喹(50毫克/千克)、雷贝拉唑(5毫克/千克)或奥美拉唑(5毫克/千克),持续6天,之后通过胆管插管收集胆汁5小时,并测定肝脏和胆汁中溶酶体酶(N - 乙酰 - β - 氨基葡萄糖苷酶和β - 半乳糖苷酶)的活性。根据N - 乙酰 - β - 氨基葡萄糖苷酶活性计算潜伏时间(肝脏溶酶体膜完整性的指标)。还测定了胆汁成分和血浆脂质浓度。氯喹给药显著增加了肝脏和胆汁中溶酶体酶的活性,但不影响溶酶体酶潜伏时间、肝脏和胆汁中的蛋白质含量或胆汁流量。它显著降低了胆汁酸水平。另一方面,雷贝拉唑和奥美拉唑给药并未改变溶酶体酶活性、溶酶体酶潜伏时间、肝脏中的蛋白质含量或肝脏重量。此外,在药物组(雷贝拉唑或奥美拉唑)和对照组之间,胆汁中溶酶体酶活性、蛋白质含量、胆汁流量、胆汁成分或血浆脂质浓度方面未观察到显著差异。本研究结果表明,雷贝拉唑与奥美拉唑一样,不影响肝脏溶酶体功能。

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