机构地区:[1]山西医科大学汾阳学院病理生理学教研室,山西汾阳032200 [2]山西医科大学汾阳学院科技中心,山西汾阳032200 [3]山西医科大学病理生理学教研室,山西太原030001
出 处:《中国病理生理杂志》2010年第1期12-16,共5页Chinese Journal of Pathophysiology
基 金:山西省归国留学人员科研基金资助项目(No.200216)
摘 要: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CCl4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 blot-ting检测结缔组织生长因子(CTGF)的表达。结果:免疫组化显示NF-κBp65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-κBp65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-κBp65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。AIM : To investigate the expression, distribution and significance of nuclear factor KB ( 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 amebecyte 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 ceils 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 wit
关 键 词:内毒素类 NF-ΚB 结缔组织生长因子 肝硬化 吡咯烷二硫代氨基甲酸盐
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