Inhibitory effects of UDCA on porcine serum-induced rat liver fibrosis
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摘要: 研究熊去氧胆酸对大鼠免疫性肝纤维化的干预作用,探讨其抗肝纤维化的机制。64只SD大鼠随机分为4组。32只大鼠腹腔内注射猪血清诱导建立肝纤维化模型;其中药物干预组16只予以熊去氧胆酸(UDCA)灌胃,余16只为模型对照组。另32只大鼠中16只给予UDCA为药物对照组,其余16只大鼠为空白对照组。于2、4、6、8周末分批处死动物,观察肝组织纤维化程度并进行免疫组化染色。发现正常肝组织不表达或微弱表达血小板衍生生长因子(PDGF-B)、组织基质金属蛋白酶抑制剂-1(TIMP-1),纤维化的肝组织PDGF-B、TIMP-1表达随肝纤维化分期的升高而增强,两者的表达呈正相关。药物干预组较模型组病理改变轻,而且肝组织PDGF-B和TIMP-1的表达下降。UDCA对大鼠免疫性肝纤维化有明显改善作用,其机制可能是抑制PDGF-B分泌及其介导的与TIMP-1增强有关的肝纤维化过程。Abstract: To observe the effect of ursodeoxycholic acid (UDCA) on fiber deposition and expression of PDGF-B, TIMP-1 in porcine serum-induced rat liver fibrosis, and to study the mechanism.64 rats were divided into model group, drug therapy group, drug contrast group and normal contrast group (16 rats in every group) .Porcine serum was injected into rat abdominal cavity to induce hepatic fibrosis model.At the time, drug therapy group and drug contrast group were given UDCA everyday until they were killed.After liver tissue was dyed with HE, the inflammatory and fibrotic degree of liver tissue and deposition change of reticular fiber were observed.The expression of PDGF-B and TIMP-1 was analyzed by immunohistochemistry.Compared with the normal contract group, the model group had shown typical hepatic fibrosis.The interval of reticular fiber had been formed extensively.Collagen in lobules of liver and hepatic sinusoid had grown up and deposited obviously.The number of reticular fiber in normal contrast group were 7.20±1.21, while those in model group 20.68±2.17 (P<0.01) .The expression of PDGF-B as well as the expression of TIMP-1 increased obviously.Drug therapy group could alleviate fibrotic severity in liver (P<0.01) and restrain the expression of PDGF-B and TIMP-1 (P<0.01) .It showed that UDCA could restrain reticular fiber and synthesis of PDGF-B and TIMP-1 so as to prevent from hepatic fibrosis in rat liver.
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Key words:
- hepatic fibrosis /
- immunity injury /
- rat /
- ursodeoxycholic acid
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