急性乙二醇中毒大鼠模型的构建及对多脏器损伤的比较  

Construction of acute ethylene glycol poisoning rat model and comparison of it's multiple organ injury

作　　者：李鑫鹏 杨凯[1] 许哲敏 杨小平 肖克来提·霍加合买提 彭鹏[1] LI Xinpeng;YANG Kai;XU Zhemin;YANG Xiaoping;Xiaokelaiti Huojiahemaiti;PENG Peng(Emergency-Trauma Center,The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China;Department of Emergency,Guangzhou First People's Hospital,Guangzhou 510180,China;Department of Critical Care Medicine,The First People's Hospital of Chongqing Liangjiang New Area,Chongqing 401121,China)

机构地区：[1]新疆医科大学第一附属医院急救创伤中心,乌鲁木齐830011 [2]广州市第一人民医院急诊科,广州510180 [3]重庆两江新区第一人民医院重症医学科,重庆401121

出　　处：《医学新知》2024年第4期372-380,共9页New Medicine

基　　金：新疆维吾尔自治区自然科学基金面上项目(2022D01C226);新疆维吾尔自治区研究生实践创新项目(XJ2023G164)。

摘　　要：目的采用灌胃法构建SD大鼠急性乙二醇(EG)中毒模型并对比分析脑、心以及肾脏损伤情况,为相关动物实验以及临床早期识别与干预提供更多参考。方法采用随机数字表法将30只SPF级SD雄性大鼠分成3组,空白对照组(NC组)10只,按12 mL·kg^(-1)灌胃生理盐水;低剂量乙二醇灌胃组(EG-L组)与高剂量乙二醇灌胃组(EG-H组)各10只,分别按12 mL·kg^(-1)剂量灌胃60%、80%乙二醇溶液。观察48 h内各组大鼠存活和死亡情况;并于造模后48 h行腹主动脉取血、处死,收集脑、心、肾等相关器官,HE染色观察脑、心、肾组织的病理变化,Pizzolato染色观察脑、肾组织中草酸钙结晶;通过平衡能力评分判断行为学改变情况;应用穿戴式心电传感器及尿量监测观察心率及尿量改变;应用酶联免疫吸附法(ELISA)检测血清中S100钙结合蛋白β(S100-β)、肌钙蛋白I(cTnI)、肾损伤分子-1(KIM-1)水平;可见光分光光度法检测各组大鼠血液中草酸水平。结果NC组、EG-L与EG-H组48 h累积生存率分别为100%、90%、70%。与NC组相比,EG灌胃两组大鼠脑、肾脏组织病理学改变明显,大鼠脑血管以及肾小管中可观察到明显草酸钙结晶沉积(P值均<0.05),且EG-H组大鼠脑血管以及肾小管中沉积量更加明显(P<0.05)。EG灌胃两组平衡能力相较NC组下降(P<0.05),其中EG-H组下降更明显(P<0.05)。与NC组相比,EG-L、EG-H组大鼠心率分别在灌胃后的第12 h、18 h、24 h、30 h加快(P值均<0.05),在30~36 h、36~42 h、42~48 h尿量均减少(P值均<0.05),而EG-H组大鼠在36~42 h、42~48 h尿量减少更显著(P<0.05)。与NC组相比,EG-L、EG-H组大鼠血清S100-β、KIM-1水平均升高(P值均<0.05),与EG-L组相比,EG-H组S100-β、KIM-1水平更高(P值均<0.05)。EG中毒的两组大鼠体内草酸含量相对于NC组均增多(P值均<0.05),且EG-H组大鼠体内草酸含量更高(P<0.05)。结论按12 mL·kg^(-1)剂量灌胃80%浓度乙二醇溶液可更好地构建EG中毒�Objective To construct a model of acute ethylene glycol poisoning in SD rats by gavage and compare the brain,heart and kidney injury,so as to provide more reference for related animal experiments and early clinical identification and intervention.Methods Thirty SPF male SD rats were divided into 3 groups by random number table method,10 rats in blank control group(NC group):gavage normal saline at 12 mL·kg^(-1);10 rats in low dose ethylene glycol gavage group(EG-L group)and 10 rats in high dose ethylene glycol gavage group(EG-H group)were gavage 60%and 80%ethylene glycol solution at 12 mL·kg^(-1).The survival and death of rats in each group were observed within 48 h;and 48 h after modeling,blood sampling from abdominal aorta was performed,and rats were sacrificed to collect brain,heart,kidney and other related organs.The pathological changes of brain,heart and kidney tissues were observed by HE staining,and the calcium oxalate crystals in brain and kidney tissues were observed by Pizzolatto staining.The behavioral changes were determined by the balance ability score.The heart rate and urine volume changes were observed by wearable electrocardiograph sensor and urine volume monitoring.The levels of S100 calcium-binding proteinβ(S100-β),troponin I(cTnI)and kidney injury molecule-1(KIM-1)in serum were detected by enzyme-linked immunosorbent assay(ELISA).The levels of oxalate in blood of rats in each group were detected by visible light spectrophotometry.Results The 48 h cumulative survival rates of NC group,EG-L group and EG-H group were 100%,90%and 70%,respectively.Compared with NC group,the pathological changes of brain and kidney tissues in EG gavage groups were obvious,and obvious calcium oxalate crystal deposition in brain vessels and renal tubules of rats were observed(all P﹤0.05),and the deposition in brain vessels and renal tubules of rats in EG-H group was more obvious(P﹤0.05).The balance ability of the two groups of rats after gavage of EG was lower than that of the NC group(P﹤0.05),and the decre

关 键 词：乙二醇 中毒 动物模型 大鼠 草酸钙 

分 类 号：R595[医药卫生—内科学] R-332[医药卫生—临床医学]