多药耐药蛋白3和法尼醇受体在婴儿胆汁淤积性肝炎肝组织中的表达及意义

Expressions of Multiple Drug Resistance 3 and Farnesoid X Receptor in Liver of Infants with Cholestatic Hepatitis and Their Clinical Significance

目的探讨婴儿胆汁淤积性肝炎肝组织中多药耐药蛋白3(MDR3)和法尼醇受体(FXR)的表达及意义。方法 2000年1月-2009年10月就诊于广西医科大学第一附属医院儿科的婴儿胆汁淤积性肝炎患儿21例。男14例,女7例,男女比例2:1;年龄(2.96±1.19)个月。收集其临床资料,进行肝组织活检。正常对照组10例,为肝移植供体,肝功能和病理检查正常。采用免疫组织化学法检测婴儿胆汁淤积性肝炎患儿及正常肝组织中MDR3、FXR的表达,通过图像分析技术进行定量分析。分析MDR3蛋白水平与血清γ-谷氨酰转肽酶及FXR蛋白水平的关系。结果 MDR3在正常肝组织的表达位于肝细胞膜,胆汁淤积性肝炎肝组织MDR3表达增强。胆汁淤积性肝炎组和正常对照组MDR3表达吸光度(A)值分别为0.13±0.02和0.11±0.03,二组比较差异有统计学意义(t=-2.239,P<0.05)。MDR3表达水平与γ-谷氨酰转肽酶水平无相关性(r=0.869,P>0.05)。正常对照组肝组织FXR表达位于肝细胞核,正常对照组和胆汁淤积性肝炎组肝组织FXR表达A值分别为0.07±0.02和0.08±0.02,二组比较差异无统计学意义(t=-1.539,P>0.05)。MDR3表达与FXR水平无相关性(r=-2.680,P>0.05)。结论在婴儿胆汁淤积性肝炎中,肝组织MDR3表达增强可能是机体的适应反应,以利于增强磷脂的转运,MDR3的上调可能与FXR无关。

Objective To explore the expressions of multiple drug resistance 3（MDR3） and farnesoid X receptor（FXR） in liver tissue of infants with cholestatic hepatitis and their clinical significance.Methods Clinic data were collected of 21 infants who were referred to the First Affiliated Hospital of Guangxi Medical University for further investigations of cholestasis hepatitis from Jan.2000 to Oct.2009,liver biopsy was performed in all patients.There were 14 male and 7 female,the male-to-female ratio was 21,and the mean age was（2.96±1.19） months.Normal liver tissues were obtained from 10 living donors of liver transplantation whose liver function and histological findings were completely normal.The expressions of MDR3 and FXR protein were examined by immunohistochemically.The image analysis technology was used to quantitatively analyze the MDR3 protein expression.Statistical correlations between the MDR3 protein expression levels and indices of blood testing and FXR protein expression were calculated.Results The normal liver showed canlicular straining for MDR3 in hepatocytes.Strong canalicular staining for MDR3 was observed in the cholestatic hepatitis liver.Optical density value of MDR3 expression in cholestatic hepatitis liver and normal control liver were 0.13±0.02 and 0.11±0.03,respectively,there was significant difference of MDR3 expression between normal liver and cholestatic hepatitis liver（t=-2.239,P0.05）.Serum level of γ-glutamyl transpeptidase were not correlated with MDR3 level（r=0.869,P0.05）.The normal liver showed nuclear localization straining for FXR in hepatocytes.Optical density va-lue of FXR expression in normal control liver and cholestatic hepatitis liver were 0.07±0.02 and 0.08±0.02,respectively,there was no significant difference of FXR expression between the cholestatic hepatitis liver and normal liver（t=-1.539,P0.05）.There was no correlation between MDR3 level and FXR level（r=-2.680,P0.05）.Conclusions In infant cholestatic hepatitis,MDR3 was up-regulated,which might represent an adaptive response aimed at the enhanced phosphatidylcholine excretion,MDR3 may not be associated with FXR.