文章摘要
丹参酮ⅡA对胆道闭锁肝纤维化大鼠SMAD4 SMAD7及I型胶原蛋白的影响
Mechanism of ligustrazine retards hepatic fibrosis via TGF-β/Smad channelin biliary atresia
投稿时间:2023-10-29  
DOI:10.3969/j.issn.1000-0399.2024.05.001
中文关键词: 丹参酮ⅡA  胆道闭锁  肝纤维化  TGF-β1/Smads通路
英文关键词: TanshinoneⅡ A  Biliary atresia  Liver fibrosis  TGF-β1/Smads pathway
基金项目:国家自然科学基金(编号:81804142)
作者单位E-mail
宋海容 450000 河南郑州 郑州大学第一附属医院检验科  
邱建利 450000 河南郑州 河南中医药大学第一附属医院儿科  
李灿灿 450000 河南郑州 河南中医药大学第一附属医院儿科  
华春兰 450000 河南郑州 郑州大学第一附属医院检验科  
段昱 450000 河南郑州 郑州大学第一附属医院检验科 zzduanyu@163.com 
摘要点击次数: 47
全文下载次数: 51
中文摘要:
      目的 探讨丹参酮ⅡA 通过调控 SMAD4、SMAD7 蛋白延缓胆道闭锁肝纤维化的机制。 方法 30 只雄性 SD 大鼠按照随机数字表法分为正常组、假手术组、模型组、吡非尼酮组(300 mg/kg)和丹参酮ⅡA 组(20 mg/kg),每组 6 只。除正常组和假手术组外,其余各组鼠采用胆总管注射无水乙醇的方法复制胆道闭锁肝纤维化模型,造模后第 1 天,吡非尼酮组和丹参酮ⅡA 组鼠给予相应药物灌胃,假手术组和模型组鼠给予等体积生理盐水(10 mL/kg)灌胃。给药 20 d 后,采用戊巴比妥钠过量麻醉动物留取标本,比较各组间大鼠血液生化指标及肝脏组织病理学改变;检测血清谷丙转氨酶、谷草转氨酶、总胆红素水平;Western blot 检测肝组织 SMAD4、SMAD7 的表达以及肝组织中 collagen I 的表达。 结果 与正常组相比,模型组大鼠血清谷丙转氨酶、谷草转氨酶、总胆红素升高(P<0.05),肝组织呈明显的纤维化改变,肝组织 SMAD4、collagen I 蛋白表达水平升高,SMAD7 表达降低(P<0.05);丹参酮ⅡA 治疗后,SMAD4、collagen I 表达水平下降,SMAD7 表达升高(P<0.05),且大鼠肝纤维化较吡非尼酮组明显减轻。 结论 丹参酮ⅡA 可以有效延缓胆道闭锁肝纤维化进展,其机制可能通过调节 TGF-β/Smads 中关键蛋白 SMAD4 及 SMAD7 的表达,从而减少肝组织中 collagen I的沉积。
英文摘要:
      Objective To investigate the mechanism of tanshinone Ⅱ A delaying hepatic fibrosis in biliary atresia by regulating SMAD4 and SMAD7 proteins. Methods Thirty male SD rats were divided into the normal group, sham operation group, model group, pirfenidone group (300 mg/kg) and tanshinone ⅡA group (20 mg/kg) according to random number table, with six rats in each group. In addition to the normal group and sham operation group, the other groups of rats were injected with anhydrous ethanol in the common bile duct to replicate the biliary atresia liver fibrosis model. On the first day after modeling, the rats in the pirfenidone group and tanshinone ⅡA group were given corresponding drugs, and the rats in the sham operation group and model group were given equal volume normal saline (10 mL/kg). After 20 days of administration, specimens were taken from animals overanesthetized with pentobarbital sodium, biochemical indexes and histopathological changes of liver were compared. Serum alanine aminotransferase, aspartate aminotransferase and total bilirubin levels were detected. Western blot analysis was performed to detect the expression of SMAD4 and SMAD7 and collagen I in liver tissue. Results Compared with normal group, serum alanine aminotransferase, aspartate aminotransferase and total bilirubin in model group were increased (P<0.05), liver tissue showed obvious fibrosis changes, collagen I and SMAD4 expression were increased, and SMAD7 expression was decreased (P<0.05). However, the expressions of SMAD4 and collagen I in the pirfenidone group and tanshinone ⅡA group decreased, while the expression of SMAD7 increased (P<0.05), and tanshinone Ⅱ A group had obvious advantages in improving liver fibrosis compared with pirfenidone group. Conclusions Tanshinone ⅡA can effectively delay the progression of liver fibrosis in biliary atresia, possibly by regulating the expression of key proteins SMAD4 and SMAD7 in TGF-β/Smads, thereby reducing the deposition of collagen I in liver tissue.
查看全文   查看/发表评论  下载PDF阅读器
关闭