摘要
目的探讨异戊酰胺(isovaleramide,ISO)在乙二醇(ethylene glycol,EG)诱导的急性中毒脑损伤大鼠模型中的保护作用及其可能的机制。方法采用随机数字表法将55只SPF级SD雄性大鼠分成4组,EG中毒组(EG组)15只:按12ml/kg灌胃80%的EG溶液;空白对照组(NC组)10只:按12ml/kg灌胃0.9%氯化钠溶液;低剂量ISO干预组、高剂量ISO干预组(EG+ISO-L、EG+ISO-H组)各15只:按12ml/kg灌胃80%的EG溶液后通过尾静脉按1ml/kg用量分别注射配置好的10、20mg/ml ISO溶液。并于造模后24h行腹主动脉取血,处死大鼠,收集大脑等相关组织,通过酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测S100钙结合蛋白β(S100-β)水平,大鼠脑组织含水量和行为学评分来判断脑水肿程度和行为学改变,HE染色及Pizzolato染色观察脑组织的病理变化与草酸钙结晶形成情况,Western blot法检测相关凋亡蛋白的表达,微量法检测各组大鼠肝内乙醇脱氢酶(alcohol dehydrogenase,ADH)活性,可见光分光光度法检测各组大鼠血液中的草酸水平。结果EG组大鼠脑组织病理学改变明显,脑血管内有草酸钙结晶形成,脑含水量增加,行为学评分降低,血清S100-β蛋白含量和凋亡蛋白表达增加(P<0.05)。EG+ISO-L、EG+ISO-H两组相较于EG组ADH活性和草酸生成量明显下降(P<0.05),大鼠脑组织病理学改变有所减轻,脑血管内草酸钙晶体较少,行为学评分增高,脑含水量、血清蛋白含量与凋亡蛋白表达较EG组减少(P<0.05)。结论ISO对急性EG中毒脑损伤大鼠具有保护作用,其机制可能与抑制ADH活性进而减少EG代谢所产生的草酸有关。
Objective To explore the protective effect of isovaleramide(ISO)in ethylene glycol(EG)-induced acute toxic brain injury rat model and its possible mechanism.Methods A total of 55 SPF SD male rats were divided into 4groups by random number table method,and 15 rats in the EG poisoning group(EG group):80%EG solution was injected into the stomach at the rate of 12ml/kg;10 rats in the blank control group(NC group):they were given 12ml/kg of normal saline;15 rats each in the low-dose ISO intervention group and the high-dose ISO intervention group(EG+ISO-L and EG+ISO-H group):they were given 80%EG solution at the rate of 12ml/kg,and then 10mg/ml and 20mg/ml ISO solution were injected through the tail vein at the rate of 1ml/kg,respectively.Blood was collected from the abdominal aorta 24hours after the modeling and sacrificed,the brain and other related tissues were collected.The level of S100 calc-binding proteinβ(S100-β),water content of the brain tissue and behavioral score of the rats were detected by enzyme-linked immunosorbent assay(ELISA)to determine the degree of cerebral edema and behavioral changes.HE staining and Pizzolato staining were used to observe the pathological changes and calcium oxalate crystal formation of the brain tissue.Western blot was used to detect the expression of related apoptotic proteins.Micromethods was used to detect the alcohol dehydrogenase(ADH)activity in liver of the rats.Visible light spectrophotometry was used to detect the level of oxalic acid in the blood of each group.Results The brain histopathological changes of EG group were obvious,calcium oxalate crystals formed in cerebral vessels,brain water content was increased,behavioral scores was decreased,serum S100-βprotein content and apoptotic protein expression were increased(P<0.05).ADH activity and oxalic acid production in EG+ISO-L and EG+ISO-H groups were significantly decreased compared with EG group(P<0.05),brain histopathological changes were alleviated,calcium oxalate crystals in cerebral vessels were less,behavioral
作者
李鑫鹏
杨凯
杨小平
许哲敏
肖克来提·霍加合买提
马雪纯
张军
彭鹏
LI Xinpeng;YANG Kai;YANG Xiaoping(Emergency-Trauma Center,First Affiliated Hospital of Xinjiang Medical University,Xinjiang 830011,China)
出处
《医学研究杂志》
2024年第4期80-85,共6页
Journal of Medical Research
基金
新疆维吾尔自治区自然科学基金资助项目(2022D01C226)
新疆维吾尔自治区研究生实践创新项目(XJ2023G164)。
关键词
乙二醇中毒
脑损伤
乙醇脱氢酶
Ethylene glycol poisoning
Brain damage
Alcohol dehydrogenase
