右美托咪定对劳力性热射病大鼠相关性横纹肌溶解的缓解及其机制  

Effect and mechanism of dexmedetomidine on alleviating heat stroke related rhabdomyolysis in rats

作　　者：李程程 刘洋 毛汉丁[2] 赵丽娜 刘树元[2] 单毅 Li Cheng-Cheng;Liu Yang;Mao Han-Ding;Zhao Li-Na;Liu Shu-Yuan;Shan Yi(School of Medicine,South China University of Technology,Guangzhou,Guangdong 510006,China;Department of Emergency Medicine,the Sixth Medical Center of Chinese PLA General Hospital,Beijing 100048,China)

机构地区：[1]华南理工大学医学院,广东广州510006 [2]解放军总医院第六医学中心急诊医学科,北京100048

出　　处：《解放军医学杂志》2024年第8期922-929,共8页Medical Journal of Chinese People's Liberation Army

基　　金：军事医学创新工程项目(18CXZ019)。

摘　　要：目的观察右美托咪定(DEX)可否通过激活肾上腺素能α_(2)受体(ADRA2A)缓解劳力性热射病(EHS)大鼠横纹肌溶解(RM),并基于活性氧(ROS)/含Pyrin结构域NOD样蛋白3(NLRP3)/白细胞介素(IL)-1β通路探索其潜在机制。方法将适应性训练7 d后的36只雄性SD大鼠随机分为6组:对照组(CN组)、EHS组、低DEX剂量组(EHS+低DEX组)、高DEX剂量组(EHS+高DEX组)、DEX联合育亨宾(YOH)组(EHS+高DEX+YOH组)、育亨宾组(EHS+YOH组);每组6只。造模前,EHS+高DEX+YOH组和EHS+YOH组腹腔注射YOH 1 mg/kg,其他4组腹腔注射等量生理盐水;造模时,除CN组外,其他5组大鼠均采用高温高湿舱内热运动法构建EHS大鼠模型,造模成功后,EHS+低DEX组大鼠腹腔注射DEX 10μg/kg,EHS+高DEX组和EHS+高DEX+YOH组大鼠腹腔注射DEX 30μg/kg,CN组、EHS组及DEX+YOH组大鼠腹腔注射等量生理盐水。6 h后麻醉,取腹主动脉血及腓肠肌组织。采用酶联免疫吸附试验(ELISA)法检测大鼠血清肿瘤坏死因子-α(TNF-α)、IL-6、IL-1β及肌红蛋白(MB)表达水平,生化试剂盒检测大鼠血清肌酸激酶(CK)水平,HE染色观察大鼠腓肠肌组织病理改变,透射电镜观察腓肠肌超显微结构改变,2′,7′-二氯荧光黄双乙酸盐(DCFH-DA)荧光探针检测活性氧(ROS)水平,Western blotting检测NLRP3、胱天蛋白酶-1(caspase-1)及肾上腺素能α_(2)受体(ADRA2A)表达水平。结果与CN组比较,EHS组大鼠血清IL-6、IL-1β、TNF-α、CK及MB均明显升高(P<0.01)。HE染色结果显示,EHS组大鼠腓肠肌组织出现纤维结构紊乱、出血、水肿、炎性细胞浸润等病理表现。透射电镜显示,EHS组腓肠肌超微结构出现肌纤维细胞肿胀、体积变大,胞质空泡化,线粒体明显肿胀、脱颗粒、双嵴消失等改变。与CN组比较,EHS组大鼠腓肠肌内ROS、NLRP3、caspase-1水平明显升高(P<0.01);与EHS组比较,EHS+低DEX组、EHS+高DEX组的TNF-α、IL-6、IL-1β、CK、MB及腓肠肌组织内ROS、NLRP3、caspase-1均呈剂�Objective To explore whether dexmedetomidine(DEX)can alleviate exertional heatstroke(EHS)-induced rhabdomyolysis(RM)in rats by activating adrenergicα_(2)receptors,and to explore its potential mechanism based on the reactive oxygen species(ROS)/NOD-like receptor protein 3(NLRP3)/interleukin-1β(IL-1β)pathway.Methods Thirty-six male Sprague-Dawley(SD)rats,after a 7-day acclimatization training,were randomly divided into six groups:control group(CN group),EHS group,low-dose DEX group(EHS+low DEX group),high-dose DEX group(EHS+high DEX group),DEX combined with yohimbine(YOH)group(EHS+high DEX+YOH group),and YOH group(EHS+YOH),with six rats in each group.Before modeling,EHS+high DEX+YOH group and EHS+YOH group were intraperitoneally injected with YOH at 1 mg/kg,while the other four groups were injected intraperitoneally with an equal dose of physiological saline(0.9%NS).During modeling,except for CN group,the other 5 groups of rats were subjected to heat exercise in a high-temperature and high-humidity chamber to construct an EHS rat model.After successful modeling,EHS+low DEX group was intraperitoneally injected with DEX at 10μg/kg,EHS+high DEX group and EHS+high DEX+YOH group were intraperitoneally injected with DEX at 30μg/kg,and CN group,EHS group and DEX+YOH group were intraperitoneally injected with equal doses of saline.After 6 h of observation,all rats were anesthetized,and their blood from the abdominal aorta and gastrocnemius muscle tissue were taken.Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression levels of serum tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1βand myoglobin(MB)in rats;biochemical assay kit was used to measure the level of creatine kinase(CK)in rat serum;HE staining was used to observe pathological changes in rat gastrocnemius muscle tissues;transmission electron microscopy was used to observe ultrastructural changes in gastrocnemius muscle;2′,7′-dichlorofluorescent yellow diacetate(DCFH-DA)fluorescent probe was used to detect the level of reactive

关 键 词：劳力性热射病 右美托咪定 含Pyrin结构域NOD样蛋白3 α_(2)肾上腺素受体 横纹肌溶解 

分 类 号：R594.13[医药卫生—内科学]