黑色素瘤缺乏因子2炎症小体介导的细胞焦亡在大鼠冷水浸泡性低体温致下丘脑损伤中的作用  

The role of absent in melanoma 2 inflammasome-mediated pyroptosis in hypothalamic injury caused by cold-water immersion hypothermia in rats

作　　者：戴晶 于新辉 王泽薇 程凤 刘颖 金红旭 Dai Jing;Yu Xinhui;Wang Zewei;Cheng Feng;Liu Ying;Jin Hongxu(College of Medicine and Biological Information Engineering,Northeastern University,Shenyang 110000,China)

机构地区：[1]东北大学医学与生物信息工程学院,辽宁沈阳110000 [2]中国医科大学北方医院,辽宁沈阳110000 [3]北部战区总医院急诊创伤实验室,辽宁沈阳110000

出　　处：《中国急救医学》2025年第3期192-198,共7页Chinese Journal of Critical Care Medicine

摘　　要：目的探讨黑色素瘤缺乏因子2(absent in melanoma 2,AIM2)炎症小体介导的细胞焦亡在大鼠冷水浸泡性低体温致下丘脑损伤中的作用。方法将20只大鼠随机分为空白组(n=10)与模型组(n=10),模型组建立冷水浸泡性低体温大鼠模型,建模过程中监测心率以评估下丘脑血供情况,应用HE染色、神经损伤评分、尼氏染色法评估下丘脑神经细胞损伤程度,Western blot、免疫荧光染色法测定下丘脑AIM2、凋亡相关斑点样蛋白(ASC)、半胱氨酸天冬氨酸蛋白酶-1(Caspase-1)、白细胞介素(IL)-1β、IL-18、焦孔素D(GSDMD)、S100钙结合蛋白β(S100β)和IL-6R等蛋白表达。结果模型组大鼠心率与核心体温变化趋势相符;模型组下丘脑神经损伤评分高于空白组(P<0.05),S100β表达高于空白组(P<0.05),脑组织病理损伤程度明显加重;与空白组比较,模型组下丘脑组织IL-1β、IL-18、IL-6R等炎症因子表达增加(P<0.05),AIM2、ASC、Caspase-1、GSDMD等焦亡相关蛋白表达增加(P<0.05)。结论冷水浸泡性低体温可诱导下丘脑损伤,该过程可能与AIM2介导的经典细胞焦亡途径有关。Objective To investigate the role of absent in melanoma 2(AIM2)inflammasome-mediated pyroptosis in hypothalamic injury induced by cold-water immersion hypothermia in rats.Methods Twenty rats were randomly divided into control group(n=10)and model group(n=10).The model group accepted cold-water immersion to establish rat models of hypothermia.During the process,the heart rate was monitored to evaluate the hypothalamic blood supply.The degree of hypothalamic nerve cell damage was evaluated by HE staining,nerve injury score and Nissl staining method.The expressions of AIM2,apoptosis-associated speck-like protein containing CARD(ASC),cysteinyl aspartate specific proteinase-1(Caspase-1),interleukin(IL)-1β,IL-18,gasdermin D(GSDMD),S100 calcium-binding protein beta(S100β)and IL-6R in hypothalamus were determined by Western blot and immunofluorescence staining method.Results The changes of heart rate and core temperature were consistent in model group.Compared with the control group,the hypothalamic nerve injury score increased in the model group(P<0.05),the expressions of S100βin hypothalamus were higher(P<0.05),and the pathological injury degree of brain tissue aggravated significantly.The expressions of IL-1β,IL-18,IL-6R in hypothalamus increased(P<0.05),and the expressions of pyroptosis-related proteins such as AIM2,ASC,Caspase-1,GSDMD increased in model group(P<0.05).Conclusions Cold-water immersion hypothermia can induce hypothalamic injury,which may be related to the classical pyroptosis pathway mediated by AIM2.

关 键 词：黑色素瘤缺乏因子2 细胞焦亡 下丘脑损伤 低体温 

分 类 号：R835[医药卫生—航空、航天与航海医学]