跨膜转运蛋白在胆汁淤积性药物性肝损伤患者肝组织中表达特点及与病理形态的相关性  

Expression characteristics of transmembrane transporters in liver tissue of patients with cholestatic drug-induced liver injury and their correlation with pathological morphology

作　　者：何晓燕 许灿[1] 何晓琳 郭立杰[2] 张海丛[2] 张向娥 叶立红[2] HE Xiaoyan;XU Can;HE Xiaolin;GUO Lijie;ZHANG Haicong;ZHANG Xiange;YE Lihong(The Second Hospital of Shijiazhuang,Shijiazhuang 050056,Hebei,China;The Fifth Hospital of Shijiazhuang,Shijiazhuang 050200,Hebei,China)

机构地区：[1]石家庄市第二医院,河北石家庄050056 [2]石家庄市第五医院,河北石家庄050200

出　　处：《现代中西医结合杂志》2022年第13期1797-1802,1807,共7页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：河北省医学科学研究重点计划课题(20171001)。

摘　　要：目的观察跨膜转运蛋白胆汁酸盐输出泵(BSEP)、多药耐药相关蛋白2(MRP2)、多药耐药糖蛋白3(MDR3)在不同病理分型胆汁淤积性药物性肝损伤患者肝组织中的表达情况及与病理形态间的关系。方法收集2015—2019年在石家庄市第二医院及石家庄市第五医院经肝穿组织病理诊断为胆汁淤积性药物性肝损伤的112例患者资料,根据肝组织病理分型将患者分为混合性肝炎组40例、淤胆性肝炎组40例、单纯性淤积组32例。比较3组患者年龄、性别构成、引起损伤的药物种类;观察3组患者肝组织病理形态特点并记录病理形态评分,免疫组化观察BSEP、MRP2、MDR3表达情况,分析BSEP、MRP2、MDR3与不同病理形态间的相关性。结果各病理亚型组患者年龄比较及<40岁患者中男女比例比较差异均无统计学意义(P均>0.05),≥40岁患者女性均显著多于男性,并且均以40~60岁女性最为多见。淤胆性肝炎组和单纯性淤积组肝细胞淤胆评分、毛细胆管胆栓评分均高于混合性肝炎组,淤胆性肝炎组羽毛样变性评分高于单纯性淤积组和混合性肝炎组,混合性肝炎组和淤胆性肝炎组小胆管损伤评分、细胆管增生评分均高于单纯性淤积组,差异均有统计学意义(P均<0.05)。BSEP、MRP2、MDR3在各病理亚型组肝细胞毛细胆管膜侧的阳性表达减少;混合性肝炎组、淤胆性肝炎组、单纯性淤积组毛细胆管胆栓评分均与MDR3积分光密度值呈中等强度负相关性(r=-0.597,P=0.021;r=-0.670,P=0.019;r=-0.706,P=0.014),肝细胞淤胆评分均与MRP2积分光密度值呈中等强度负相关性(r=-0.634,P=0.017;r=-0.786,P=0.013;r=-0.463,P=0.026),羽毛样变性评分均与BSEP积分光密度值呈中等强度负相关性(r=-0.793,P=0.012;r=-0.788,P=0.013;r=-0.544,P=0.026)。结论BSEP、MRP2、MDR3在不同病理分型胆汁淤积性药物性肝损伤患者肝组织中均呈低表达,三者不同表达强度可引起不同病理形态,是药物性�Objective It is to observe the expression of transmembrane transporter bile salt export pump(BSEP),multidrug resistance-related protein 2(MRP2)and multidrug resistance glycoprotein 3(MDR3)in liver tissue of patients with different pathological types of cholestatic drug-induced liver injury and its relationship with pathological morphology.Methods The data of 112 patients with cholestatic drug-induced liver injury diagnosed by liver biopsy in the Second Hospital of Shijiazhuang and the Fifth Hospital of Shijiazhuang from 2015 to 2019 were collected.The patients were divided into mixed hepatitis group(40 cases),cholestatic hepatitis group(40 cases)and simple stasis group(32 cases)according to liver histopathological classification.The age,gender composition,and the types of drugs causing injury were compared among the three groups;the pathological characteristics of liver tissue in the three groups were observed and the pathological scores were recorded;the expressions of BSEP,MRP2,and MDR3 were observed by immunohistochemistry;the correlation between BSEP,MRP2,MDR3 and different pathological type was analyzed.Results There was no significant difference in the age of patients among each pathological subtype group and in the proportion of males and females among patients under 40 years old(all P>0.05),women were significantly more than men in the patients aged≥40 years old,and women aged 40-60 years old were the most common.The scores of hepatocellular cholestasis and capillary bile thrombus in the cholestatic hepatitis group and the simple stasis group were higher than those in the mixed hepatitis group,the scores of feathery degeneration in the cholestatic hepatitis group were higher than that in the simple stasis group and the mixed hepatitis group,the scores of small bile duct injury and bile duct hyperplasia in the mixed hepatitis group and the cholestatic hepatitis group were higher than those in the simple stasis group,and the differences were all statistically significant(all P<0.05).The positive expressio

关 键 词：胆汁淤积 药物性肝损伤 跨膜转运蛋白 

分 类 号：R575[医药卫生—消化系统]