一次性腹腔注射环磷酰胺致卵巢储备功能下降模型大鼠意外死亡的病理分析

Pathological analysis of one-time intraperitoneal injection of cyclophosphamide on accidental death of rats modeled with diminished ovarian reserve

目的 基于病理学观察探析一次性腹腔注射环磷酰胺致卵巢储备功能下降(diminished ovarian reserve,DOR)模型大鼠意外死亡的影响。方法 将动情周期正常的雌性未孕SD大鼠60只,按随机数字表法分为空白对照组10只和造模组50只,造模组大鼠使用一次性腹腔注射环磷酰胺90mg/kg,空白对照组大鼠注射相同剂量0.9%生理盐水。分别于注射环磷酰胺前和注射后第1周、第2周测量两组大鼠体重;对意外死亡大鼠立即解剖,肉眼观察其内脏大体形态学变化,并摘取双肺、心脏、肝脏、胃及双侧肾脏进行HE染色,于光镜下观察意外死亡大鼠重要器官病理形态学改变。结果 实验期间空白对照组大鼠体重逐渐增长,未出现死亡大鼠;造模组大鼠体重逐渐下降,与空白对照组大鼠相比差异有统计学意义(P <0.001),并于腹腔注射环磷酰胺后至灌胃前共计12只大鼠死亡,死亡率为24.00%(12/50)。对意外死亡大鼠重要脏器进行HE染色病理学观察发现与对照组相比,造模组大鼠肺组织呈广泛淤血,肺泡间隔增宽,肺上皮细胞水肿改变;胃浅表黏膜糜烂,浅表上皮细胞脱落。结论 一次性腹腔注射环磷酰胺诱导DOR模型可使大鼠出现肺和胃的损伤,可能对造模组大鼠的意外死亡有重要影响。

Objective To explore the effects of one-time intraperitoneal injection of cyclophosphamide on accidental death of rats modeled with diminished ovarian reserve(DOR)based on pathological observations.Methods Sixty non-pregnant female SD rats during the normal estrous cycle were divided into a blank control group(n=10)and a model group(n=50)according to random number table.Rats in the model group were given one-time intraperitoneal injection of cyclophosphamide at 90 mg/kg,while rats in the blank group were injected with 0.9%normal saline at the same dose.The body weight of rats in two groups was measured before injection and at the first week as well as the second week after injection of cyclophosphamide,respectively.The rats that died accidentally were dissected immediately and the gross morphological changes of their viscera were observed by naked eye.The lungs,heart,liver,stomach and kidneys of died rats were collected for HE staining,and the pathological changes of their important organs were observed under the light microscope.Results During experiment,the weight of rats in the blank control group increased gradually,and no rats died.The weight of rats in the model group decreased gradually,and the difference in weight between two groups was statistically significant(P<0.001).A total of 12 rats in the model group died after intraperitoneal injection of cyclophosphamide and before intragastric administration,with a mortality rate of 24.00%(12/50).Important organs of the rats that died by accident were pathologically observed after HE staining.The observation results showed that,compared with those of the blank group,the rats in the model group had extensive congestion in the lung tissue,widened alveolar septum,edema of pulmonary epithelial cells,erosion of superficial gastric mucosa as well as shedding of gastric superficial epithelial cells.Conclusion Modeling DOR induced by one-time intraperitoneal injection of cyclophosphamide can cause lung and stomach injury in rats,which may have an important influence on the accidental death of rats in the model group.