CAJ | 학술논문

目的: 研究核转录因子-κB(NF-κB)在实验性肝纤维化过程中的表达、分布及意义.方法: 雌性Wistar大鼠随机分为正常组、肝纤维化模型组和NF-κB抑制剂吡咯烷二硫代氨基甲酸盐(PDTC)组,PDTC组大鼠在给CCl_4的同时给予PDTC灌胃.肝组织羟脯氨酸(Hyp)含量测定,鲎试剂法测定血浆内毒素水平,赖氏法测定丙氨酸氨基转移酶(ALT),TBA法检测丙二醛(MDA)的水平,免疫组化法测定NF-κB的表达,Western blotting检测结缔组织生长因子(CTGF)的表达.结果: 免疫组化显示NF-κB p65在正常肝组织中少量表达于中央静脉周围的肝细胞胞浆内,肝纤维化模型组肝组织可见程度不等的细胞浆和(或)细胞核表达,主要分布于纤维化区、肝窦区、血管壁及部分胆管细胞、变性肝细胞也可见阳性染色,阳性细胞数从第1周末就显著高于正常对照组,PDTC组阳性细胞数明显低于同期肝纤维化模型组(P<0.05);肝纤维化模型组内毒素含量、NF-κB以及CTGF表达明显升高,且两两均呈正相关;PDTC组内毒素含量呈先升高后降低趋势,NF-κB p65和CTGF表达显著低于同期肝纤维化模型组,且二者呈正相关(r=0.815, P<0.01),内毒素与NF-κB p65和CTGF表达无相关性.结论: 内毒素可能通过激活NF-κB通路上调CTGF的表达.
목적: 연구핵전록인자-κB(NF-κB)재실험성간섬유화과정중적표체、분포급의의.방법: 자성Wistar대서수궤분위정상조、간섬유화모형조화NF-κB억제제필각완이류대안기갑산염(PDTC)조,PDTC조대서재급CCl_4적동시급여PDTC관위.간조직간포안산(Hyp)함량측정,후시제법측정혈장내독소수평,뢰씨법측정병안산안기전이매(ALT),TBA법검측병이철(MDA)적수평,면역조화법측정NF-κB적표체,Western blotting검측결체조직생장인자(CTGF)적표체.결과: 면역조화현시NF-κB p65재정상간조직중소량표체우중앙정맥주위적간세포포장내,간섬유화모형조간조직가견정도불등적세포장화(혹)세포핵표체,주요분포우섬유화구、간두구、혈관벽급부분담관세포、변성간세포야가견양성염색,양성세포수종제1주말취현저고우정상대조조,PDTC조양성세포수명현저우동기간섬유화모형조(P<0.05);간섬유화모형조내독소함량、NF-κB이급CTGF표체명현승고,차량량균정정상관;PDTC조내독소함량정선승고후강저추세,NF-κB p65화CTGF표체현저저우동기간섬유화모형조,차이자정정상관(r=0.815, P<0.01),내독소여NF-κB p65화CTGF표체무상관성.결론: 내독소가능통과격활NF-κB통로상조CTGF적표체.
AIM: To investigate the expression, distribution and significance of nuclear factor κB (NF-κB) in experimental hepatic fibrosis.METHODS: Wistar rats were randomly divided into normal control group, hepatic fibrisis model group and the pyrrolidine-1-dithiocarboxylic acid ammonium sail (PDTC) group. The PDTC group was treated with subcutaneous injection of carboan tetrachloride, and treated with PDTC by oral administration. The content of hydroxyproline was measured. Endotoxin was determined with a Limulus amebocyte lysate test kit. The alanine aminotransferase (ALT) in plasma was measured by laishi method. The content of malondialdehyde (MDA) in liver tissue was detected by means of TBA method. The expression of NF-κB was determined by immunohistochemistry. The expression of connective tissue growth factor (CTGF) was measured by Western blotting.RESULTS: In control group, just a small amount of NF-κB p65 was expressed in the cytoplasm of a few hepatocytes around central veins. In model group, the positive staining of NF-κB p65 was expressed in cytoplasm and nucleus, mainly in fibrous stepta, hepatic sinusoid and partial vascular endothelial cells, part of proliferating ductular epithelial cells and impaired hepatocytes. The positive staining began to increase from the first week. The expression of NF-κB in the liver tissues in PDTC group was lower than that in model control group (P<0.05). The ET levels and expression of NF-κB and CTGF began to increase significantly in liver fibrosis group. The levels of plasma ET and expression of NF-κB and CTGF were correlated positively with each other. In PDTC group, ET content in plasma increased significantly at first, then began to decline at the end of the test. The expression of NF-κB and CTGF in liver tissues in PDTC groups was lower than that in model group. Furthermore, the expression of NF-κB in liver tissues in PDTC group was correlated positively with CTGF. The levels of plasma ET were not correlated with the expression of NF-κB and CTGF.CONCLUSION: ET may up-regulate the expression of CTGF by activating NF-κB.