右美托咪定对腹腔镜气腹大鼠肠屏障功能及肠道菌群的影响  

Effect of Dexmedetomidine on Intestinal Barrier Function and Intestinal Microbiota in Laparoscopic Pneumoperitoneum Rats

作　　者：宁夏青 王会英 张暖暖 王佳琦 李雪琴 蒋聪聪 翟帆 张士霞[1] NING Xiaqing;WANG Huiying;ZHANG Nuannuan;WANG Jiaqi;LI Xueqin;JIANG Congcong;ZHAI Fan;ZHANG Shixia(College of Veterinary Medicine,Hebei Agricultural University,Baoding 071000,China;Anyang Animal Disease Prevention and Control Center,Anyang 455000,China)

机构地区：[1]河北农业大学动物医学院,保定071000 [2]安阳市动物疫病预防控制中心,安阳455000

出　　处：《中国畜牧兽医》2024年第7期3176-3184,共9页China Animal Husbandry & Veterinary Medicine

基　　金：国家自然科学基金(31802250);河北省教育厅科学研究项目(BJ2019053、QN2015184);河北省自然科学基金(C2023204085)。

摘　　要：【目的】探究右美托咪定(dexmedetomidine, DEX)对腹腔镜气腹大鼠肠屏障功能及肠道菌群的影响。【方法】试验将30只SD大鼠随机分为3组:假手术组(Sham)(n=6)、CO_(2)气腹组(CO_(2))(n=12)、DEX组(n=12)。CO_(2)和DEX组大鼠在气腹前30 min分别腹腔注射1 mL/kg生理盐水和50μg/kg右美托咪定,随后在15 mmHg气腹压力下维持90 min建立气腹模型。Sham组不通气腹,其余操作同CO_(2)组。气腹结束后12、24 h采集大鼠回肠组织,观察其组织病理形态学变化,并通过试剂盒测定大鼠回肠组织中丙二醛(MDA)、谷胱甘肽(GSH)、白细胞介素6(IL-6)、IL-1β、肿瘤坏死因子-α(TNF-α)含量以及髓过氧化物酶(MPO)活性;利用实时荧光定量PCR检测闭锁小带蛋白-1(ZO-1)、封闭蛋白1(Claudin-1)、闭合蛋白(Occludin)的mRNA相对表达量;采集回肠组织内容物,通过高通量双端测序检测大鼠回肠菌群的变化。【结果】与Sham组相比,CO_(2)组大鼠回肠组织结构紊乱,肠绒毛变形,出现炎性细胞浸润等现象;结肠中MDA、IL-6、IL-1β、TNF-α含量及MPO活性均极显著升高(P<0.01),GSH含量以及ZO-1、Occludin、Claudin-1基因mRNA表达量均极显著降低(P<0.01);肠道菌群多样性减少,门水平上,厚壁菌门(Firmicutes)相对丰度有降低趋势(P>0.05),放线菌门(Actinobacteria)、变形菌门(Proteobacteria)相对丰度有增加趋势(P>0.05)。属水平上,乳杆菌属(Lactobacillus)和异杆菌属(Allobaculum)相对丰度有降低趋势(P>0.05),而双歧杆菌属(Bifidobacterium)相对丰度有增加趋势(P>0.05)。与CO_(2)组相比,DEX组大鼠回肠组织结构紊乱及肠绒毛变形情况缓解,炎性细胞浸润减少。结肠中GSH含量及ZO-1、Claudin-1、Occludin基因mRNA表达量均极显著或显著升高(P<0.01;P<0.05),MDA、IL-6、IL-1β、TNF-α含量及MPO活性均显著或极显著降低(P<0.05;P<0.01);肠道菌群多样性增加,门水平上,厚壁菌门相对丰度有增加趋势(P>0.05),放线菌门、变形菌�【Objective】The purpose of this study was to investigate the effects of dexmedetomidine(DEX)on intestinal barrier function and intestinal microbiota in rats undergoing laparoscopic pneumoperitoneum.【Method】Thirty SD rats were randomly divided into three groups:Sham group(n=6),CO_(2)pneumoperitoneum group(CO_(2))(n=12)and DEX group(n=12).The rats in CO_(2)and DEX groups were intraperitoneally injected with 1 mL/kg normal saline and 50μg/kg DEX 30 min before pneumoperitoneum,respectively,and then maintained at 15 mmHg pneumoperitoneum pressure for 90 min to establish an pneumoperitoneum model.Pneumoperitoneum was impassable in Sham group,and other operations were the same as those in CO_(2)group.The ileum tissues were collected 12 and 24 h after pneumoperitoneum,and the histopathologic changes were observed.The contents of malondialdehyde(MDA),glutathione(GSH),interleukin-6(IL-6),IL-1β,tumor necrosis factor-α(TNF-α)and myeloperoxidase(MPO)activity of ileum in rats were determined by the kit.The mRNA relative expression of occlusive zonal-1(ZO-1),occlusive protein-1(Claudin-1)and occlusive protein(Occludin)was detected by Real-time quantitative PCR.The contents of ileal tissue were collected and the changes of ileal microflora were detected by high-throughput paired-end sequencing.【Result】Compared with Sham group,the structure of ileum was disordered,intestinal villi deformed and inflammatory cell infiltrated in CO_(2)group.MDA,IL-6,IL-1βand TNF-αcontents,and MPO activity were extremely significantly increased(P<0.01),GSH content and mRNA expression of ZO-1,Occludin,Claudin-1 genes were extremely significantly decreased(P<0.01).The diversity of intestinal flora decreased.At the phylum level,the relative abundance of Firmicutes showed a decreasing trend(P>0.05),while the relative abundance of Actinobacteria and Proteobacteria showed an increasing trend(P>0.05).At the genus level,the relative abundance of Lactobacillus and Allobaculum showed a decreasing trend(P>0.05),while the relative abundance of B

关 键 词：右美托咪定 CO_(2)气腹 氧化应激 肠屏障 肠道菌群 

分 类 号：S854.5[农业科学—临床兽医学]