右美托咪定对烧伤大鼠肠道屏障损伤时蛋白质组学的影响  

Effect of dexmedetomidine on proteomics during intestinal barrier injury in burned rats

作　　者：秦超 骆宁 韩庆庆 于泳浩[1] Qin Chao;Luo Ning;Han Qingqing;Yu Yonghao(Department of Anesthesiology,Tianjin Medical University General Hospital Tianjin Research Institute of Anesthesiology,Tianjin 300052,China)

机构地区：[1]天津医科大学总医院麻醉科,天津市麻醉学研究所,天津300052

出　　处：《中华麻醉学杂志》2023年第8期996-1001,共6页Chinese Journal of Anesthesiology

摘　　要：目的:评价右美托咪定对烧伤大鼠肠道屏障损伤时蛋白质组学的影响。方法:清洁级健康成年雄性SD大鼠64只,体质量250~300 g,8~12周龄,采用随机数字表法分为4组(n=16):假手术组(Sham组)、假手术+右美托咪定组(Sham-Dex组)、烧伤组(Burn组)和烧伤+右美托咪定组(Burn-Dex组)。Burn组和Burn-Dex组制备大鼠背部(约40%全身体表面积)Ⅲ度烧伤模型,Sham组和Sham-Dex组大鼠仅背部脱毛用烫头以皮温接触。Sham-Dex组和Burn-Dex组大鼠在造模后分别静脉输注右美托咪定5μg·kg^(-1)·h^(-1)3 h,Sham组和Burn组大鼠连续输注相同剂量0.9%生理盐水。于停药后6 h时采集大鼠腹主动脉血,随后处死大鼠取肠组织,采用HE染色法观察肠组织病理学结果并行Chiu评分,测定血浆荧光素异硫氰酸酯-葡聚糖(FITC-Dextran)和二胺氧化酶(DAO)浓度。对肠组织蛋白质进行同位素相对和绝对定量标记、液质联用-串联质谱分析,筛选差异表达蛋白质,对差异表达蛋白进行STRING蛋白质互作网络分析、基因本体分析(GO)和KEGG通路分析。结果:与Sham组比较,Burn组和Burn-Dex组烧伤后大鼠肠组织Chiu评分和停药后6 h时血浆FITC-Dextran和DAO浓度升高(P<0.05);与Burn组比较,Burn-Dex组烧伤后大鼠肠组织Chiu评分和停药后6 h时血浆FITC-Dextran和DAO浓度降低(P<0.05)。通过STRING蛋白质互作网络分析、GO分析和KEGG通路分析得出满足条件的蛋白质基因为Psmb10、Psmb7、RGD1310507和LOC100909441,其中Psmb10和Psmb7存在相互作用,且在蛋白酶体等多种途径中显著富集。结论:右美托咪定可引起烧伤大鼠肠道屏障损伤时蛋白表达的变化,Psmb10和Psmb7可能是其作用靶点。Objective To evaluate the effects of dexmedetomidine on proteomics during intestinal barrier injury in burned rats.Methods Sixty-four clean-grade healthy adult male Sprague-Dawley rats,aged 8-12 weeks,weighing 250-300 g,were divided into 4 groups(n=16 each)by the random number table method:sham operation group(Sham group),sham operation plus dexmedetomidine group(Sham-Dex group),burn group(Burn group)and burn plus dexmedetomidine group(Burn-Dex group).Rats were subjected toⅢdegree burn covering 40%of the total body surface area on back in Burn group and Burn-Dex group,and the back hair was removed and then the rats were exposed to skin temperature with a perm in Sham group and Sham-Dex group.Dexmedetomidine 5μg·kg^(-1)·h^(-1) was intravenously infused for 3 h after developing the model in Sham-Dex group and Burn-Dex group.The equal volume of 0.9%normal saline was continuously infused in Sham group and Burn group.Blood from the abdominal aorta was collected at 6 h after stopping administration,then the rats were sacrificed,and intestinal tissues were obtained for examination of pathological changes(HE staining method)and for determination of plasma fluoresce in isothiocyanate-dextran and diamine oxidase(DAO)concentrations.Intestinal damage was assessed and scored according to Chiu.The relative and absolute quantitative isotope labeling and LC-tandem mass spectrometry were performed to screen the differentially expressed proteins.The differentially expressed proteins were analyzed by STRING protein interaction network analysis,gene ontology analysis and KEGG pathway analysis.Results Compared with Sham group,the Chiu′s score after burn and plasma concentrations of FITC-Dextran and DAO at 6 h after stopping administration were significantly increased in Burn and Burn-Dex groups(P<0.05).Compared with Burn group,the Chiu′s score after burn and plasma concentrations of FITC-Dextran and DAO at 6 h after stopping administration were significantly decreased in Burn-Dex group(P<0.05).Analysis of STRING protein inte

关 键 词：右美托咪啶 烧伤 肠黏膜 蛋白质组学 

分 类 号：R614[医药卫生—麻醉学]