血晶素通过调控血红素加氧酶-1／核转录因子-κB的表达抗肝纤维化  

Hemin regulates the expression of nuclear factor kappa B of heme oxygenase -1 in hepatic fibrosis

作　　者：杨慧[1] 张丽[1] 张晓倩 张晓华 赵龙凤[1] Yang Hui;Zhang Li;Zhang Xiaoqian;Zhang Xiaohua;Zhao Longfeng(Department of Infectious Diseases,First Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学第一医院感染病科,太原030001

出　　处：《中华肝脏病杂志》2018年第9期654-659,共6页Chinese Journal of Hepatology

基　　金：山西省卫生计生委科研项目（201601030）;山西省研究生优秀创新项目（20103050）

摘　　要：目的观察血晶素（Heroin）在大鼠肝纤维化进展过程中的治疗效果并探讨其相关作用机制。方法将60只雄性Wistar大鼠随机分为正常对照组、4周模型组、6周模型组、血红素加氧酶-1（HO-1）抑制剂锌原卟啉-IX（ZnPP-IX）干预组、Hemin干预组，在复合因素构建肝纤维化模型过程中，干预组自第4周起开始给予隔日腹腔注射ZnPP-IX或Hemin干预2周。采用实时定量聚合酶链反应检测肝组织HO-1、α-平滑肌肌动蛋白（仅-SMA）及核转录因子-κB（NF-κB）的mRNA表达；采用免疫组织化学技术检测HO-1及α-SMA定位表达；酶联免疫吸附法测定检测血清透明质酸、Ⅲ型胶原前肽及肝组织转化生长因子D（TGFp）、白细胞介素6（IL-6）的表达；碱水解法检测肝组织羟脯氨酸（Hyp）含量。应用单因素方差分析（One-wayANOVA）进行各组样本均数的比较，两组间差异比较采用两独立样本的t检验，P〈0．05为差异有统计学意义。结果Hemin的干预同模型组及ZnPP-IX处理组相比可显著促进肝组织中HO-1的mRNA表达（P〈0．01）及蛋白分布，而α-SMA的mRNA表达（P〈0．05）及在汇管区、纤维间隔与肝窦周围分布明显减少，Hyp含量及血清中透明质酸、Ⅲ型胶原前肽水平均显著下降（P〈0．05）；同时Hemin干预组NF-κBp65的mRNA表达及其下游TGFD、IL-6的产生也受到抑制护〈0．05）。结论血晶素可以显著抑制大鼠肝纤维化进展，该作用同其上调HO-1表达，进而抑制NF-κBp65的活性及下游炎性因子的释放密切相关。Objective To observe the therapeutic effects and related mechanism of hemin on the progression of hepatic fibrosis in rats. Methods Sixty male Wistar rats were randomly divided into normal control group, 4-week model group, 6-week model group, hemin inhibitor zinc protoporphyrin-IX （ZnPP-IX） intervention group and hemin intervention group. Hemin intervention group in complex liver fibrosis model was intraperitonealy administered ZnPP-IX or hernin every other day for 2 weeks from the fourth week. The mRNA expression of HO-1, or-smooth muscle actin （α-SMA） and nuclear factor-riB （NF-κB） in the liver tissue was detected by real-time polymerase chain reaction. Immunohistochemistry was used to detect HO-1 and localization of α-SMA expression. Serum hyaluronic acid, propeptide of type III collagen and hepatic transforming growth factor beta （TGFβ）, and interleukin 6 （IL-6） expressions were detected by enzyme-linked immunosorbent assay. The content of hydroxyproline in hepatic tissues was measured by alkaline hydrolysis method. One-way ANOVA was used to compare the mean of each group. The difference between the twogroups was compared by independent samples t- test. P-values 〈 0.05 was considered statistically significant. Results Compared with model groups and ZnPP-IX intervention group, Hemin＇s intervention significantly increased the expression of HO-1 mRNA （P 〈 0.01） and protein distribution in liver tissues, while the expression of alpha-SMA mRNA was significantly decreased （P 〈 0.05） in portal space and areas around the fibrotic septum, and hepatic sinus. Hyp content and serum hyaluronic acid and propeptide of type III collagen decreased significantly （P 〈 0.05）. Meanwhile, NF-κB p65 mRNA expression and the downstream production of TGFβ and IL-6 in Hemin intervention group were also inhibited （P 〈 0.05）. Conclusion Hemin can significantly inhibit the progression of hepatic fibrosis in rats by up-regulating HO-1 expression, and the inhibiting activity of NF-κB p

关 键 词：肝硬化 血红素加氧酶-1 血晶素 核转录因子-ΚB 

分 类 号：R575.2[医药卫生—消化系统]