雷贝拉唑钠对Beagle犬脏器毒性的研究-东南大学学报医学版

雷贝拉唑钠对Beagle犬脏器毒性的研究

单位：东南大学医学院药理学系, 江苏南京 210009

分类号：R392.18;R-33

出版年·卷·期（页码）：2018·37·第四期（696-700）

摘要：

目的：研究不同剂量注射用雷贝拉唑钠对Beagle犬脏器的损害。方法：将Beagle犬随机分为生理盐水对照组，注射用雷贝拉唑钠1、5、25 mg·kg^-1·d^-1组，每组6只，雌雄各半。给药4周，观察Beagle犬的生命体征、体质量变化、血细胞及血生化改变、尿常规以及内脏重量和病理改变。结果：生理盐水对照组与注射用雷贝拉唑钠低剂量组Beagle犬均未出现任何中毒症状，而给药组中高剂量组Beagle犬出现流涎和双眼结膜充血等中毒症状，高剂量组雌雄犬血液学检查结果均出现红细胞、白细胞和血小板数减少，且Beagle犬肝脏质量和肝脏器系数呈剂量依赖性的增加。组织病理学检查结果表明高剂量组胃黏膜下层固有腺体可见轻度萎缩和炎症细胞浸润；甲状腺组织疏松，滤泡上皮呈扁平状略有增生，胶质较少。上述改变在犬恢复期有明显好转和减轻。结论：静脉注射高剂量（25 mg·kg^-1·d^-1）雷贝拉唑钠对Beagle犬脏器有损害，肝、消化腺（胃腺）、甲状腺为毒性靶器官，但毒性症状和器官组织学改变在停药10 d后恢复；无任何毒性症状的雷贝拉唑钠安全剂量为1 mg·kg^-1·d^-1。

Objective:To study the damage of different doses of rabeprazole sodium injection to viscera of Beagle dogs. Methods:Beagle dogs were randomly divided into normal saline group and injection with rabeprazole sodium groups (1, 5 and 25 mg·kg^-1·d^-1). Each group had 6 dogs, 3 male and 3 female. Beagle dog's vital signs, weight changes, blood cells and biochemical changes, urine routines and visceral weight and pathological changes were observed for 4 weeks. Results:Neither the control group of normal saline nor the low dose group of rabelazole sodium for injection showed any poisoning symptoms in Beagle dogs. After administration, the Beagle dogs in the medium and high dose group appeared toxic symptoms, such as salivation and binocular conjunctival congestion. The hematological examination results of male and female Beagle dogs in the high dose group showed decreased erythrocyte, leukocyte and platelet count. The liver weight and liver organ coefficient of Beagle dogs increased in a dose-dependent manner. Histopathological examination revealed the glands underlying the stomach lining showed mild atrophy and inflammatory cell infiltration. The thyroid tissue was less colloid in the high dose group. However, the above-mentioned changes were significantly improved and alleviated during the recovery period. Conclusion:There is viscera damage in Beagle dogs of high rabeprazole sodium dose group. Liver, digestive gland (stomach gland), thyroid are the toxic target organs of rabeprazole sodium. Toxic symptoms and organ histologic changes recover 10 days after withdrawal of the drug, and the safe dose of no toxicity is 1 mg·kg^-1·d^-1.

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