高迁移率族蛋白1在钬激光致输尿管狭窄患者中的作用及甘草酸苷的体外抑制研究  

Role of high mobility group protein 1 in patients with ureteral stricture induced by holmium laser and inhibitory effect of glycyrrhizin in vitro

作　　者：陈柯宇 王亮[3] CHEN Ke-Yu;WANG Liang(Department of Urology,the Affiliated Hospital of Southwest Medical University,Luzhou 646000,China)

机构地区：[1]西南医科大学附属医院泌尿外科,泸州646000 [2]四川省什邡市人民医院泌尿外科,什邡618400 [3]西部战区总医院泌尿外科,成都610083

出　　处：《中国免疫学杂志》2020年第13期1631-1635,共5页Chinese Journal of Immunology

摘　　要：目的:探讨高迁移率族蛋白1(HMGB1)在钬激光致输尿管狭窄患者中的作用及甘草酸苷的体外抑制效应。方法:选取28例钬激光致输尿管狭窄患者作为研究对象,均行输尿管狭窄段切除术,荧光定量聚合酶链式反应(qRT-PCR)检测输尿管狭窄段组织中HMGB1、IL-1β、肿瘤坏死因子-α(TNF-α)、转化生长因子-β1(TGF-β1)mRNA水平,Pearson法分析HMGB1与各因子的相关性。将人输尿管上皮SV-HUC-1细胞随机分为3组,即对照组、钬激光组、钬激光+甘草酸苷组。照射48 h后,Western blot检测HMGB1及下游TLR4/NFκB信号通路的表达;ELISA检测上清中IL-1β、TNF-α、TGF-β1、Ⅰ型胶原蛋白、纤维连接蛋白的含量;免疫荧光染色检测E-cadherin和Vimentin表达情况。结果:HMGB1 mRNA表达与IL-1β、TNF-α、TGF-β1 mRNA水平呈正相关(P<0.05)。对照组、钬激光+甘草酸苷组细胞中HMGB1、TLR4、p-NFκB蛋白表达量均低于钬激光组(P<0.05)。对照组、钬激光+甘草酸苷组细胞上清液中IL-1β、TNF-α、TGF-β1、Ⅰ型胶原蛋白、纤维连接蛋白含量均低于钬激光组(P<0.05)。与钬激光组相比较,对照组、钬激光+甘草酸苷组细胞E-cadherin荧光强度明显增强,Vimentin荧光强度明显减弱。结论:在钬激光致输尿管狭窄患者的输尿管组织中,HMGB1表达与促炎及促纤维化因子水平呈正相关。在钬激光照射输尿管上皮细胞的体外模型中,甘草酸苷可抑制HMGB1及其下游TLR4/NFκB信号通路的激活,下调炎症及纤维化因子的表达,抑制细胞发生上皮间质转化。Objective:To explore the role of high mobility group protein 1(HMGB1)in patients with ureteral stricture induced by holmium laser and the inhibitory effect of glycyrrhizin in vitro.Methods:Twenty-eight patients with ureteral stricture induced by holmium laser were selected as the study subjects.All patients underwent ureteral stricture segment resection.Quantitative real time polymerase chain reaction(qRT-PCR)was used to detect the mRNA levels of HMGB1,IL-1β,tumor necrosis factor-α(TNF-α)and transforming growth factor-β1(TGF-β1)in ureteral stricture tissue.Pearson method was used to analyze the correlation between HMGB1 and various factors.Human ureteric epithelial SV-HUC-1 cells were randomly divided into three groups:control group,holmium laser group and holmium laser+glycyrrhizin group.After 48 hours of irradiation,the expression of HMGB1 and downstream TLR4/NF-κB signaling pathway was detected by Western blot;the contents of IL-1β,TNF-α,TGF-β1,collagenⅠand fibronectin in supernatant were detected by ELISA;and the expression of E-cadherin and Vimentin was detected by immunofluorescence staining.Results:The expression of HMGB1 mRNA was positively correlated with the levels of IL-1β,TNF-αand TGF-β1(P<0.05).The expression levels of HMGB1,TLR4 and p-NF-κB in control group and holmium laser+glycyrrhizin group were lower than those in holmium laser group(P<0.05).The contents of IL-1β,TNF-α,TGF-β1,collagen I and fibronectin in supernatant of control group and holmium laser+glycyrrhizin group were lower than those of holmium laser group(P<0.05).Compared with holmium laser group,the fluorescence intensity of E-cadherin in control group and holmium laser+glycyrrhizin group increased significantly,while the fluorescence intensity of Vimentin decreased significantly.Conclusion:The expression of HMGB1 is positively correlated with the levels of pro-inflammatory and pro-fibrotic factors in ureteral tissues of patients with ureteral stricture induced by holmium laser.Glycyrrhizin can inhibit the activation

关 键 词：钬激光 输尿管狭窄 高迁移率族蛋白1 甘草酸苷 炎症 纤维化 上皮间质转化 

分 类 号：R693.2[医药卫生—泌尿科学]