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作 者:刘清华[1] 李定国[1] 宗春华[1] 黄新[1] 徐芹芳[1] 陆汉明[1]
机构地区:[1]上海第二医科大学新华医院消化内科,上海200092
出 处:《上海第二医科大学学报》2005年第1期39-42,共4页Acta Universitatis Medicinalis Secondae Shanghai
基 金:国家自然科学基金(30170411)资助项目.
摘 要:目的探讨体内睾酮(T)和雌激素(β-Est)抑制肝纤维化的关系。方法CCl4皮下注射诱导肝纤维化模型,观察20μg·kg-1·d-1β-Est对完整或去势雄性大鼠肝纤维化形成的影响。以标准酶、ELISA、RIA分别测定血清肝功能、细胞外基质(ECM)和性激素水平;VG胶原染色观察肝组织病理学改变,结合图像分析计算胶原面积;RT-PCR和免疫组化检测转化生长因子-β1(TGF-β1)、激活素BA(ACTβA)在组织中的表达。结果β-Est能改善去势纤维化大鼠肝功能,降低ECM分泌、肝组织纤维化程度和TGF-β1、ACTβA表达,而对完整雄性大鼠肝纤维化形成无影响;两组大鼠血清雌二醇水平无显著性差异。结论β-Est能抑制肝纤维化形成,T影响其发挥保护作用,可能是造成肝纤维化性别差异原因之一。Objective To evaluate the relationship between serum testosterone (T) and anti-fibrogenesis of 17β-estradiol (β-Est). Methods Liver fibrosis was induced by CCl4 administration. The fibrosis-suppressive effect of β-Est (20 μg·kg-1·d-1 ) was evaluated in the intact or gonadectomized male rat model. The serum levels of liver enzyme, extracelluar matrix (ECM) and sex hormone were determined by standard enzymatic methods, ELISA and RIA, respectively; the degrees of fibrosis in the liver were determined by VG stain; transforming growth factor-β1 (TGF-β1 ) and activin βA( ACTβA) expressions in the liver were studied by immunohistochemistry and semiquantita-tive RT-PCR. Results All the changes made it clear that β-Est treatment could improve the serum levels of liver enzyme, reduce ECM secretion, suppress hepatic collagen deposition and decrease TGF-β1 and ACTβA expression in the gonadectomized male rat model significantly, but not in the intact male rat model despite attaining the same serum estradiol ( E2 ) levels. Conclusion β-Est could reduce CCl4-induced hepatic fibrosis in rats, but the resistance to the protective effects of estrogen in the male appears to depend on the presence of testosterone. This may be one reason for the sex associated differences in the progression from hepatic fibrosis to cirrhosis.
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