右美托咪定对二氧化碳气腹大鼠ET-1、ICAM-1表达及肾脏缺血性损伤的影响  

Effects of Dexmedetomidine on the Expressions of ET-1,ICAM-1 and Renal Ischemic Injury in Carbon Dioxide Pneumoperitoneum Rats

作　　者：杨毅 杨男 黎娟娟 付莉娟 郭祯华 贺文伟 YANG Yi;YANG Nan;LI Juan-juan;FU Li-juan;GUO Zhen-hua;HE Wen-wei(Department of Anesthesiology,the No.1 Affiliated Hospital of Dali University,Dali 671000,China)

机构地区：[1]大理大学第一附属医院麻醉科,云南大理671000

出　　处：《药物生物技术》2021年第6期590-594,共5页Pharmaceutical Biotechnology

基　　金：云南省教育厅科学研究基金项目(No.2019J0777)。

摘　　要：探讨右美托咪定(Dex)对二氧化碳气腹(Pp)大鼠肾组织内皮素-1(ET-1)、细胞间黏附分子-1(ICAM-1)表达及肾脏缺血性损伤的影响,探究其保护作用机制。选用SD雄性大鼠50只,随机分为假手术(Sham)组、Pp组、Dex低(1μg/kg)、中(5μg/kg)、高(25μg/kg)剂量组,每组10只。除Sham组外,其余各组均通过设置Pp压力20 mmHg持续2 h建立Pp模型。除Sham组和Pp组经腹腔注射生理盐水外,Dex各剂量组经腹腔给予相应剂量Dex溶液。各组给药24 h后,处死大鼠,取大鼠腹主动脉血及肾组织标本,用酶联免疫吸附法(ELISA)检测肾功能指标血清肌酐(Scr)和尿素氮(BUN)含量、肾组织炎症因子白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)含量及氧化应激指标超氧化物歧化酶(SOD)、丙二醛(MDA)含量;用苏木精-伊红染色(HE)检测大鼠肾组织肾小管空泡、变性等病理损伤程度;用蛋白免疫印迹法(Western blot)检测肾组织ET-1、ICAM-1蛋白表达情况。与Sham组相比,Pp组大鼠肾组织可见肾小管上皮细胞肿胀、空泡变性、肾小管管腔扩张、肾间质炎症细胞浸润等病理损伤,血清Scr和BUN含量、肾组织IL-6、TNF-α、MDA含量及ET-1、ICAM-1蛋白表达等均升高(P<0.05),肾组织SOD含量降低(P<0.05);与Pp组相比,Dex低、中、高剂量组肾组织病理损伤减轻,血清Scr和BUN含量、肾组织IL-6、TNF-α、MDA含量及ET-1、ICAM-1蛋白表达等均降低(P<0.05),肾组织SOD含量均升高(P<0.05),且Dex各剂量组上述指标呈剂量依赖性降低。Dex可降低Pp大鼠肾组织氧化应激反应,抑制ICAM-1及ET-1蛋白表达,降低炎症细胞与内皮细胞黏附,改善肾组织损伤。To investigate the effects of dexmedetomidine(Dex)on the expression of endothelin-1(ET-1),intercellular adhesion molecule-1(ICAM-1)and renal ischemic injury in carbon dioxide pneumoperitoneum(Pp)rats,and to explore its protective mechanism.50 male SD rats were randomly divided into Sham group,Pp group,Dex low(1μg/kg),medium(5μg/kg)and high(25μg/kg)dose groups,with 10 rats in each groups.Except Sham group,all the other groups established the model of Pp by setting the pressure of 20 mmHg for 2 hours.Sham group and Pp group were injected with normal saline through abdominal cavity,in addition,Dex groups were given the corresponding dose of Dex solution.After 24 hours of administration,the rats were killed and the abdominal aorta blood and renal tissue samples were taken,the contents of serum creatinine(Scr)and urea nitrogen(BUN),inflammatory factors of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α),oxidative stress indexes of superoxide dismutase(SOD)and malondialdehyde(MDA)were measured with enzyme-linked immunosorbent assay(ELISA).The degree of renal tubule cavitation and degeneration was detetced with hematoxylin eosin staining(HE);And the expression of ET-1 and ICAM-1 in renal tissue was detected with Western blot.Compared with the Sham group,the renal tissue of the Pp group showed the renal tubular epithelial cell swelling,vacuolation,tubuloluminal expansion,interstitial inflammatory cell infiltration and other pathological injury,the contents of serum Scr and BUN,the contents of IL-6,TNF-αand MDA,the expression of ET-1 and ICAM-1 proteins in renal tissue were higher(P<0.05),and the content of SOD in renal tissue was lower(P<0.05).Compared with Pp group,the pathological injury of renal tissue in Dex low,middle and high dose groups was alleviated,the contents of serum Scr and BUN,the contents of IL-6,TNF-αand MDA,the expression of ET-1 and ICAM-1 proteins in renal tissue were lower(P<0.05),the content of SOD in renal tissue was higher(P<0.05),and the above indexes in Dex groups decreased in a dose

关 键 词：右美托咪定 二氧化碳气腹 肾脏缺血性损伤 内皮素-1 细胞间黏附分子-1 大鼠 

分 类 号：R971.3[医药卫生—药品]