ICAM-1在急性膀胱扩张诱导的大鼠肾氧化损伤中的作用机制研究  

Study on the mechanism of ICAM-1 in rat kidney oxidative damage induced by acute bladder dilatation

作　　者：廖肇州 袁野 钟勇 李军 高生慧 林陈 LIAO Zhao-zhou;YUAN Ye;ZHONG Yong(Department of Urology,Chongqing Thirteenth People's Hospital,Chongqing 400053,China)

机构地区：[1]重庆市第十三人民医院泌尿外科,重庆400053

出　　处：《临床和实验医学杂志》2020年第18期1908-1912,共5页Journal of Clinical and Experimental Medicine

基　　金：重庆卫生计生委中医药科技项目(编号:ZY201802125)。

摘　　要：目的探讨血管紧张素Ⅱ-1型(AT1)受体介导的细胞间黏附分子1(ICAM-1)在急性膀胱扩张(AUBD)导致大鼠肾氧化损伤中的作用及机制。方法30只雌性SD大鼠根据随机数字表法分为对照组、AUBD组、AUBD+血管紧张素Ⅱ受体阻断剂(ARB)组,每组10只。对照组大鼠只进行充盈性膀胱测压。AUBD组大鼠用2倍正常膀胱容量充盈膀胱2 h,在排空后1 h进行充盈性膀胱测压。AUBD+ARB组大鼠在膀胱排空前10 min肾内注射2 mg/kg的AT1受体阻断剂缬沙坦,其余处理同AUBD组。检测各组大鼠膀胱顺应性、不稳定收缩频率以及膀胱和肾组织中活性氧(ROS)、还原型辅酶Ⅱ(NADPH)氧化酶和过氧化物酶含量,苏木精-伊红染色和免疫组化检测各组大鼠肾形态学、巨噬细胞浸润和ICAM-1表达。结果与AUBD组(0.018±0.006 ml/cmH 2O)对比,AUBD+ARB组(0.057±0.014 ml/cmH 2O)大鼠膀胱顺应性显著增加,而不稳定收缩频率(6.81±1.405次/10 min vs.2.65±0.813次/10 min)显著降低,差异均具有统计学意义(P<0.05)。与过度充盈前对比,AUBD组(0.114±0.013 ml/cmH 2O vs.0.018±0.006 ml/cmH 2O)和AUBD+ARB组(0.113±0.020 ml/cmH 2O vs.0.057±0.014 ml/cmH 2O)大鼠过度充盈后膀胱顺应性显著降低,而不稳定收缩频率(AUBD组:0.56±0.019次/10 min vs.6.81±1.405次/10 min;AUBD+ARB组:0.43±0.027次/10 min vs.2.65±0.813次/10 min)显著增加,差异均具有统计学意义(P<0.05)。与对照组对比,AUBD组大鼠膀胱和肾组织中ROS(膀胱:215.72±36.81;肾:141.93±12.75)、NADPH氧化酶(膀胱:9.46±1.28 ml/cmH 2O;肾:5.34±1.21 ml/cmH 2O)和过氧化物酶(膀胱:4.85±0.91μmol·min^-1·g^-1;肾:4.85±0.91μmol·min^-1·g^-1)含量显著增加,AUBD组(ROS:膀胱1146.29±59.45,肾846.48±43.71;NADPH氧化酶:膀胱17.39±1.53,肾19.62±1.68;过氧化物酶:膀胱27.47±3.16μmol·min^-1·g^-1,肾27.47±3.16μmol·min^-1·g^-1)显著低于AUBD+ARB组(ROS:膀胱597.66±46.84,肾511.64±49.69;NADPH氧化酶:膀胱12.74±1.55μmol·min^-1·g^-1,肾9.51±1Objective To investigate the role and mechanism of Intercellular adhesion molecule 1(ICAM-1)mediated by angiotensinⅡtype 1(AT1)receptors in acute bladder distension(AUBD)-induced renal oxidative damage in rats.Methods Thirty female SD rats were randomly divided into control group,AUBD group,and AUBD+ARB group according to the random number table method,with 10 rats in each group.The rats in the control group only performed filling bladder manometry.In the AUBD group,the bladder of rats was filled with twice the normal bladder capacity for 2 h,and the bladder pressure was measured 1 h after emptying.Rats in the AUBD+ARB group were injected with 2 mg/kg of AT1 receptor blocker valsartan in the kidney 10 minutes before bladder emptying,and the rest of the treatment was the same as in the AUBD group.The bladder compliance,unstable contraction frequency,and reactive oxygen species(ROS),nicotinamide adenine dinucleotide phosphate(NADPH)oxidase and peroxidase contents in bladder and kidney tissues were detected in each group.Hematoxylin-eosin(HE)staining and immunohistochemistry were used to detect kidney morphology,macrophage infiltration and ICAM-1 expression in each group.Results Compared with the AUBD group(0.018±0.006 ml/cmH 2O),the bladder compliance of the AUBD+ARB group(0.018±0.006 ml/cmH 2O)was significantly increased(P<0.05),and the frequency of unstable contractions(6.81±1.405 times/10 min vs.2.65±0.813 times/10 min)was significantly reduced(P<0.05).Compared with those before overfilling,the bladder compliance of the AUBD group(0.114±0.013 ml/cmH 2O vs.0.018±0.006 ml/cmH 2O)and the AUBD+ARB group(0.113±0.020 ml/cmH 2O vs.0.057±0.014 ml/cmH 2O)after overfilling were decreased significantly(P<0.05),and the frequency of unstable contractions(AUBD group:0.56±0.019 times/10 min vs.6.81±1.405 times/10 min;AUBD+ARB group:0.43±0.027 times/10 min vs.2.65±0.813 times/10 min)was increased significantly(P<0.05).Compared with the control group,the contents of ROS(bladder:215.72±36.81;kidney:141.93±12.75),N

关 键 词：大鼠 急性膀胱扩张 血管紧张素Ⅱ-1型 细胞间黏附分子1 肾氧化损伤 机制 

分 类 号：R694[医药卫生—泌尿科学]