米尔贝肟大鼠急性中毒的病理学研究

以SD大鼠为研究对象,采用一次性灌胃给药法进行米尔贝肟的急性毒性试验,研究了试验大鼠对米尔贝肟的毒性反应和病理变化.结果显示,米尔贝肟对SD大鼠具有雄雌差异性,半数致死量(LD50)分别为2002、1131 mg/kg·BW.大鼠急性中毒4h后,出现明显的临床症状,主要表现为共济失调、立毛、精神委靡、呼吸困难、食欲减退,且呈明显的量效关系.组织病理学变化主要为肝脏中央静脉淤血,肝索排列紊乱,肝细胞颗粒变性；肺淤血；肾小管上皮细胞和消化道黏膜上皮颗粒变性、坏死；脾脏淤血；大脑皮层血管炎症细胞浸润,边缘空泡化.根据WHO外源性急性毒性分级标准,米尔贝肟属低毒化学物.米尔贝肟急性中毒后会广泛损害大鼠肝、肺、肾和肠等多种组织器官,甚至引起这些组织器官的变性坏死,并可对神经组织造成一定的损伤.

PATHOLOGY OF MILBEMYCIN OXIME IN INDUCING ACUTE TOXICITY IN SPRAGUE-DAWLEY RATS

The acute toxicity of milbemycin oxime was examined in Sprague-Dawley(SD) rats.Rats were intragastrically administered with milbemycin oxime and clinical signs and histopathological changes were observed.The median lethal dose(LD50) significant differed between male and female rats,2002mg/kg or 1131 mg/kg body weight,respectively.Clinical signs developed at 4 hours post administration,including ataxia,piloerection,depression,dyspneic respiration and loss of appetite.These clinical signs were dose-dependent.Histopathological alterations included congested central veins of livers,granular degeneration of the hepatocytes,congested lungs and spleens,degeneration and necrosis of the epithelium of renal tubules and intestines,and infiltration of inflammatory cells and rimmed vacuoles in cerebral cortexes.In summary,milbemycin oxime caused acute toxicity,damaging livers,lungs,kidneys,intestines and other organs of SD rats and even caused the destruction of these organs.The nerve tissues were also impaired.Milbemycin oxime was classified into low-toxicity chemical category according to the WHO grading standards.