右美托咪定上调低氧诱导因子-1ɑ对脓毒症大鼠肠黏膜屏障损伤的保护作用  

Protection effect of dexmedetomidine against sepsis-induced intestinal mucosal barrier injury by up-regulating hypoxia inducible factor-1ɑin rats

作　　者：李会 李俊 黄素琴 李玉红 范俊 LI Hui;LI Jun;HUAN Suqin;LI Yuhong;FAN Jun(Department of Anesthesiology,Shulan(Hangzhou)Hospital,Hangzhou 310004,Zhejiang,China;Department of Anesthesiology,Shulan(Hangzhou)Hospital,Shulan International Medical College,Zhejiang Shuren University,Hangzhou 310004,Zhejiang,China;Department of Anesthesiology,Jinjiang City Hospital(Shulan Medical Jinjiang Hospital),Jinjiang 362200,Fujian,China)

机构地区：[1]树兰(杭州)医院麻醉科,浙江杭州310004 [2]浙江树人大学树兰国际医学院树兰(杭州)医院麻醉科,浙江杭州310004 [3]晋江市医院(树兰医疗晋江医院)麻醉科,福建晋江362200

出　　处：《中国临床药理学与治疗学》2021年第12期1386-1392,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：浙江省科学技术厅公益项目(LY21H150001);绍兴市医药卫生科技计划项目(2020A13014);浙江省医药卫生科技计划项目(2020KY329);浙江省医学会基金(2018ZYC-A46);济南微生态生物医学省实验室科研项目资助。

摘　　要：目的:探索右美托咪定(DEX)对脓毒症大鼠肠黏膜屏障损伤的保护作用及机制。方法:随机将48只SD大鼠分成4组(n=12):假手术组(sham组)、脓毒症组(sepsis组)、sepsis+右美托咪定组(DEX组)以及sepsis+DEX+HIF-1ɑ抑制剂(Bay87-2243组)。用盲肠结扎穿孔(cecal ligation and perforation,CLP)建立脓毒症模型,DEX组和Bay87-2243组分别于CLP前30 min和CLP后2 h腹腔注射DEX 30μg/kg;Bay87-2243组于CLP前连续3 d口服灌胃Bay87-22439 mg/kg。其他组腹腔注射和口服等量生理盐水。Western blot检测大鼠肠黏膜组织中HIF-1ɑ和紧密连接蛋白(tight junction protein,TJs)表达;ELISA检测大鼠血浆二胺氧化酶(DAO)、肠型脂肪酸结合蛋白(FABP2)和D-乳酸(D-LAC)血浆浓度;HE染色检测大鼠肠黏膜形态学改变。结果:DEX可显著上调脓毒症损伤大鼠肠黏膜组织的HIF-1ɑ表达水平(P<0.05),从而改善脓毒症大鼠的肠黏膜病理损伤、降低Chiu's评分(P<0.05),降低肠黏膜通透性(P<0.05),上调TJs蛋白(P<0.05);且上述作用可被HIF-1ɑ抑制剂Bay87-2243逆转。结论:DEX上调肠黏膜组织HIF-1ɑ蛋白水平对脓毒症大鼠肠黏膜损伤具有保护作用。AIM:To explore the protective effect and mechanism of dexmedetomidine on intestinal mucosal barrier injury in septic rats.METHODS:Forty eight SD rats were randomly divided into four groups(n=12):sham operation group(sham group),sepsis group(sepsis group),sepsis+dexmedetomidine group(DEX group),and sepsis+DEX+HIF-1ɑinhibitor Bay87-2243(Bay87-2243 group).Sepsis model was established by cecal ligation and perforation(CLP).The rats in both DEX and Bay87-2243 groups were given 30μg/kg of DEX intraperitoneally 30 minutes before CLP and 2 hours after CLP;while the rats in Bay87-2243 group received oral gavage of Bay87-2243(9 mg/kg)for 3 days before CLP.The other groups were intraperitoneally injected and orally with the same amount of normal saline.The HIF-1ɑand the tight junction protein(tight junction protein,TJs)was detected by western blot;the plasma concentrations of diamine oxidase(DAO),intestinal fatty acid binding protein(FABP2)and D-lactic acid(D-LAC)were detected by ELISA;the morphological changes of intestinal mucosa were detected by HE staining.RESULTS:DEX significantly increased the expression level of HIF-1ɑ(P<0.05)on intestinal mucosa in rats with sepsis injury(P<0.05),thus ameliorated intestinal mucosal pathological injury,reduced Chiu's score(P<0.05),decreased intestinal mucosal permeability(P<0.05),and up-regulated TJs protein expression(P<0.05).Moreover,effect on sepsis induced intestinal mucosal injury of DEX was reversed by HIF-1ɑBay87-2243.CONCLUSION:DEX could protect against sepsis-induced intestinal mucosal injury by up-regulating HIF-1ɑexpression in rats.

关 键 词：脓毒症 右美托咪定 HIF-1ɑ 紧密连接蛋白 肠黏膜通透性 

分 类 号：R363.274[医药卫生—病理学]