Rho激酶抑制剂对脓毒症肝损伤的影响  

Effects of Rho kinase inhibitors on septic liver injury

作　　者：邢博民 郭娜 宁海慧 丁新耘 马玉清[2] XING Bomin;GUO Na;NING Haihui;DING Xinyun;MA Yuqing(The First Clinical Medical College of Lanzhou University,Lanzhou 730000,Gansu,China;Department of Anesthesiology,the First Hospital of Lanzhou University,Lanzhou 730000,Gansu,China)

机构地区：[1]兰州大学第一临床医学院,甘肃兰州730000 [2]兰州大学第一医院麻醉科,甘肃兰州730000

出　　处：《中国临床药理学与治疗学》2022年第5期544-550,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：甘肃省自然科学基金(21JR1RA077)。

摘　　要：目的:探讨Rho激酶抑制剂Y-27632对脓毒症急性肝损伤的作用。方法:健康成年雄性SD大鼠32只,随机分为假手术组(Sham组)、假手术+Y-27632组(Sham+Y组),盲肠结扎穿孔组(CLP组)和CLP+Y-27632组(CLP+Y组),每组8只。采用CLP方法制备大鼠脓毒症模型,造模24 h心脏采血后安乐死大鼠,收集血清及肝脏组织。苏木精-伊红(HE)染色观察各组大鼠肝组织病理学变化;蛋白质免疫印迹(Western blot)检测各组大鼠肝组织ROCK1和下游NF-κB蛋白的表达情况;免疫组织化学法(ICH)检测大鼠肝脏组织ROCK1蛋白表达;酶联免疫吸附(ELISA)法检测各组大鼠血清肝功能指标ALT、AST水平及肝组织匀浆IL-18、IL-10和谷胱甘肽(GSH)含量变化。结果:与Sham组相比,Sham+Y组肝脏组织病理学无明显变化,CLP组肝细胞排列紊乱,有大量炎症细胞浸润,CLP+Y组炎症细胞浸润较少,肝细胞条索逐渐恢复。与Sham组相比,CLP和CLP+Y组ROCK1蛋白表达增加(P<0.05);与CLP组相比,CLP+Y组ROCK1蛋白表达减少(P<0.05)。与Sham组相比,CLP和CLP+Y组NF-κB蛋白表达增加(P<0.05);与CLP组相比,CLP+Y组NF-κB蛋白表达减少(P<0.05);ICH检测到Sham组肝脏ROCK1少量表达,CLP组和CLP+Y组大量表达;与Sham组相比,CLP和CLP+Y组血清ALT、AST水平升高(P<0.05),与CLP组相比,CLP+Y组ALT、AST水平降低(P<0.05)。与Sham组相比,CLP和CLP+Y组肝组织匀浆IL-18含量升高(P<0.05),CLP组肝组织匀浆IL-10和GSH含量降低(P<0.05),CLP+Y组IL-10和GSH的变化相近(P>0.05);与CLP组相比,CLP+Y组IL-18含量降低(P<0.05),IL-10和GSH含量升高(P<0.05)。结论:Rho激酶抑制剂可以减轻脓毒症大鼠急性肝损伤,可能与抑制Rho/ROCK/NF-κB信号通路及其下游的炎症因子,减轻肝脏炎症反应,同时降低肝脏氧化应激水平有关。AIM:To investigate the effect of Rho kinase inhibitor Y-27632 on acute liver injury in sepsis.METHODS:Thirty-two healthy adult male SD rats were randomly divided into sham operation group(Sham group),sham operation+Y-27632 group(Sham+Y group),cecal ligation and perforation group(CLP group)and CLP+Y-27632 group(CLP+Y-27632 group),8 animals in each group.The rat sepsis model was established by the CLP method,and the rat was euthanized 24 hours after the model was established,and the serum and liver tissue were collected.Hematoxylin-eosin(HE)staining was used to observe the pathological changes in the liver tissue of the rats in each group;Western Blot was used to detect the expressions of ROCK1 and downstream NF-κB proteins in the liver tissue of the rats in each group;immunohistochemical method The expression of ROCK1 protein in liver tissue of rats was detected;enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of serum liver function indexes ALT and AST,and the changes of IL-18,IL-10 and GSH contents in liver tissue homogenate.RESULTS:Compared with the Sham group,there was no significant change in the histopathology of the liver in the Sham+Y group.In the CLP group,the arrangement of hepatocytes was disordered,with a large number of inflammatory cells infiltrating.Compared with the Sham group,the expression of ROCK1 protein in the CLP and CLP+Y groups was increased(P<0.05);compared with the CLP group,the ROCK1 protein expression in the CLP+Y group was decreased(P<0.05).Compared with the Sham group,the expression of NF-κB protein in the CLP and CLP+Y groups increased(P<0.05);compared with the CLP group,the NF-κB protein expression in the CLP+Y group decreased(P<0.05);A small amount of expression was found in the liver Sham group,and a large amount was expressed in the CLP group and CLP+Y group;compared with the Sham group,the serum ALT and AST levels in the CLP and CLP+Y groups were increased(P<0.05).The levels of ALT and AST in+Y group decreased(P<0.05).Compared with the Sham group,t

关 键 词：脓毒症 肝损伤 ROCK1蛋白 Y-27632 

分 类 号：R965.2[医药卫生—药理学]