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目的连续28 d对SD大鼠经口给予吴茱萸Evodia rutaecarpa(Juss)Benth醇提物,观察可能的毒性反应性质、程度及可逆性,判断毒性靶器官。方法雌雄各半80只SD大鼠随机分4组,每组20只,分别给予20.83、6.66、2.50 g生药/kg·d吴茱萸醇提物和生理盐水,1次/d,连续28 d。给药结束、恢复14 d后各组解剖10只。解剖时称重脏器,腹主动脉采血进行血常规、生化检测,组织器官进行光镜、电镜检查。结果 (1)肝脏:给药动物肝肥大,无光泽,质脆;给药组肝脑比呈剂量依赖性改变,停药14 d后恢复;光镜下高剂量组肝细胞变性肿胀、炎细胞浸润(8/8),病变分级高于对照组(P<0.0083),恢复期缓解;电镜下高剂量组肝细胞线粒体肿胀、内质网扩张,肝血窦内皮细胞有空泡,恢复期缓解。(2)血液系统:高剂量组红细胞及血红蛋白降低,有贫血征象,同时网织红细胞代偿性升高,恢复期未完全恢复。(3)心脏:电镜检查高剂量组心肌细胞肌丝紊乱、内质网扩张、线粒体肿胀,恢复期未好转,中低剂量组无明显异常,但恢复期加重。(4)肾脏:电镜检查高剂量组肾足细胞肿胀,肾小球系膜弯曲及肾小球血管内皮细胞肿胀,恢复期好转。结论肝、血液系统为吴茱萸醇提物明确毒性靶器官;电镜检查心脏和肾脏有损伤,为可疑毒性靶器官。
OBJECTIVE To observe the toxicity, degree and reversibility of evodia rutaecarpa (Juss) Benth ethanol extract of Evodia rutaecarpa (Juss) Benth to SD rats for 28 consecutive days. Methods 80 male and female SD rats were randomly divided into 4 groups with 20 rats in each group. The animals were given 20.83, 6.66 and 2.50 g crude drug / kg · d of Evodia rutaecarpa ethanol and saline once a day for 28 consecutive days. At the end of dosing, 10 rabbits in each group were restored after 14 days of recovery. Anatomy, weighing organs, abdominal aorta blood for blood tests, biochemical tests, tissues and organs light microscopy, electron microscopy. The results showed that: (1) Liver: The liver of the treated animals was hypertrophic, dull and crisp; the liver-to-brain ratio of the administration group changed in a dose-dependent manner and recovered after 14 days of drug withdrawal; (8/8), the pathological grade was higher than that of the control group (P <0.0083), and the recovery period was relieved. The mitochondria swelling and endoplasmic reticulum of liver cells in high-dose group were vacuolized and the recovery period was relieved . (2) blood system: high-dose group of red blood cells and hemoglobin decreased, there are signs of anemia, while reticulocyte compensatory increase in recovery did not fully recover. (3) Heart: Electron microscopy examination of high-dose group of myocardial cell filament disorders, endoplasmic reticulum dilation, mitochondria swelling, recovery did not improve, low-dose group no obvious abnormalities, but the recovery period increased. (4) The kidneys: electron microscopy examination of high-dose group of renal podocyte swelling, mesangial flexion and glomerular capillary endothelial cell swelling, recovery period improved. Conclusion The hepatic and hematological systems are the specific toxic target organs of Ethanol extract of Evodia. Electron microscopy can damage the heart and kidneys and may be suspected target organ of toxicity.