氯雷他定治疗脂多糖诱导的大鼠肝纤维化的作用及其机制  

Effect of loratadine on lipopolysaccharide-induced hepatic fibrosis in rats and its mechanism

作　　者：邢露露 高幸 黄惠娟 潘延凤[1] Xing Lulu;Gao Xing;Huang Huijuan;Pan Yanfeng(Department of Infection,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院感染科,郑州450052

出　　处：《中华实验外科杂志》2023年第2期254-257,共4页Chinese Journal of Experimental Surgery

基　　金：河南省教育厅项目(20A320063);河南省医学科技项目(SB201901026)。

摘　　要：目的探讨氯雷他定治疗大鼠肝纤维化的作用及其机制。方法采用随机分组方式将18只8周龄雄性SD大鼠分成对照组、模型组和氯雷他定组,每组6只。模型组和氯雷他定组大鼠长期使用脂多糖(3 mg/kg)诱导肝纤维化,随后氯雷他定组大鼠使用氯雷他定(10 mg/kg)治疗肝纤维化,模型组和对照组大鼠使用0.9%生理盐水灌胃处理。观察大鼠肝脏形态学及组织学变化;检测大鼠血液指标肝功能水平和氧化应激指标;用酶联免疫吸附试验(ELISA)法检测肝脏组织炎症指标及胶原沉积指标;用实时定量聚合酶链反应(Real-time PCR)法检测肝纤维化相关因子;原位末端标记法(TUNEL)检测细胞凋亡水平;马松(Masson)染色检测肝脏胶原沉积面积。多组间比较采取单因素方差分析。结果(1)模型组大鼠肝功能丙氨酸氨基转移酶(ALT)、天冬氨酸转氨酶(AST)指标水平[(89.24±7.25)、(224.35±59.31)U/L]显著高于对照组[(67.51±14.67)、(140.11±22.21)U/L],氯雷他定组大鼠肝功能ALT、AST指标水平[(74.23±7.33)、(176.32±8.15)U/L]显著低于模型组(F=6.930、7.884,P<0.05)。(2)模型组大鼠肝组织炎症指标肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)水平[(253.83±57.78)、(576.10±248.83)pg/ml]显著高于对照组[(193.58±73.55)、(457.14±116.34)pg/ml],氯雷他定组大鼠肝组织炎症指标指标TNF-α、IL-1β水平[(86.16±57.62)、(240.10±88.18)pg/ml]低于模型组(F=10.763、6.277,P<0.05)。(3)模型组大鼠血清氧化应激指标超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平[(319.25±99.24)U/ml、(127.31±6.91)U]显著低于对照组[(425.91±19.64)U/ml、(163.23±24.67)U],氯雷他定组大鼠血清SOD、GSH-Px水平[(410.09±49.69)U/ml、(171.18±19.34)U]高于模型组(F=4.695、9.545,P<0.05)。(4)模型组大鼠肝脏组织中凋亡细胞数量[(26.38±16.21)个]高于对照组[(2.98±1.70)个],氯雷他定组大鼠凋亡细胞数量[(4.60±4.32)个]低于模型组(F=6Objective To investigate the effect and mechanism of loratadine on hepatic fibrosis in rats.Methods The total of 18-week-old male SD rats were randomly divided into control group,model group and loratadine group,with 6 rats in each group.Model group and loratadine group were treated with lipopolysaccharide(3 mg/kg)to induce liver fibrosis for a long time,and then loratadine group was treated with loratadine(10 mg/kg)to treat liver fibrosis.Model group and control group were treated with 0.9%normal saline intragastrically.The morphological and histological changes of rat liver were observed.Blood index,liver function level and oxidative stress index of rats were detected.Liver inflammation and collagen deposition were detected by enzyme-linked immunosorbent assay(ELISA).The factors related to liver fibrosis were analyzed by real-time quantitative polymerase chain reaction(Real-time PCR).Apoptosis was detected by in situ end labeling(TUNEL).Masson staining was used to detect collagen deposition area in liver.One-way analysis of variance was used to compare groups.Results(1)The levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in model group[(89.24±7.25),(224.35±59.31)U/L]were significantly higher than those in control group[(67.51±14.67),(140.11±22.21)U/L],while the levels of ALT and AST in loratadine group[(74.23±7.33),(176.32±8.15)U/L]were significantly lower than those in model group(F=6.930,7.884,P<0.05).(2)The levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in liver tissue inflammation in model group[(253.83±57.78),(576.10±248.83)pg/ml]were significantly higher than those in control group[(193.58±73.55),(457.14±116.34)pg/ml],and the levels of TNF-αand IL-1βin liver tissue inflammation in loratadine group[(86.16±57.62),(240.10±88.18)pg/ml]were lower than those in model group(F=10.763,6.277,P<0.05).(3)The levels of serum oxidative stress indexes[superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)]in model group[(319.25±99.24)U/ml,(127.31±6.91)U

关 键 词：氯雷他定 脂多糖 肝纤维化 

分 类 号：R575.2[医药卫生—消化系统]