清毒汤对重症肝损伤大鼠肠道黏膜通透性的影响
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摘要
目的观察清毒汤对重症肝损伤大鼠肠道黏膜通透性的影响,探讨该方治疗慢性重型肝炎(chronic severe hepatitis,CSH)的作用机制。方法建立硫代乙酰胺(thioacetamide,TAA)致重症肝损伤大鼠模型,以清毒汤进行干预治疗,采用血液生化法、ELISA法、Western Blot法,观察其对该模型大鼠肝功能的总胆红素(total bilirubin,TBIL)、谷草转氨酶(aspartate transaminase,AST)和反映肠道黏膜通透性的二胺氧化酶(diamine oxidase,DAO)、闭锁连接蛋白-1(zonula occludens-1,ZO-1)及肠组织白细胞介素(interleukin,IL)-1β、IL-6的影响。结果 (1)与模型组相比较,乳果糖组及清毒汤小、中剂量组大鼠中TBIL、AST、DAO含量显著性下降(P<0.01);ZO-1蛋白的表达水平在所有治疗组中均有显著性升高(P<0.01);乳果糖组、清毒汤中剂量组IL-1β、IL-6的含量均显著性降低(P<0.01);(2)与乳果糖比较,清毒汤中剂量组TBIL、AST、DAO、IL-1β含量明显下降(P<0.05)及ZO-1表达水平显著性升高(P<0.01);清毒汤小剂量组中IL-6呈明显下降(P<0.05);清毒汤大剂量组中AST、DAO有显著性统计学差异(P<0.01)。结论清毒汤能降低重症肝损伤大鼠肠道黏膜的通透性,从而改善肝功能,其作用机制可能是减少有害物质穿过肠道黏膜屏障,进而减少其通过肝肠循环途径而加重肝损伤的发生机率。
Objective To observe the effect of Qingdu decoction on intestinal mucosal permeability in rats with severe liver injury,and to explore the mechanism of it to treat chronic severe hepatitis( CSH). Methods Severe liver injury model was establish by thioacetamide( TAA),and Qingdu decoction was used to treat them,then blood biochemical method,ELISA,Western Blot was used to observe theeffect of total bilirubin( TBIL),aspartate aminotransferase( AST) which reflect liver function,and diamine oxidase( DAO),blocking binding protein-1( ZO-1) and interleukin of intestinal tissue( IL-1,IL-6) which reflect intestinal mucosal permeability of this model rats. Results( 1) Compared with the model group,the level of TBIL,AST,DAO in the lactulose group,the low and medium dose groups of Qingdu decoction were significantly decreased( P < 0. 01); the expression level of ZO-1 protein in all treatment groups were significantly increased( P < 0. 01); the level of IL-1β and IL-6 in lactulose group and the Qingdu decoction medium dose group were significantly decreased( P < 0. 01);( 2) Compared with the lactulose group,the level of TBIL,AST,DAO,IL-1β in the Qingdu decoction medium dose group was decreased obviously( P< 0. 05),the expression level of ZO-1 was increased significantly( P < 0. 01); IL-6 in the Qingdu decoction low dose group was decreased obviously( P < 0. 05); AST,DAO in the Qingdu decoction high dose group had significantly statistical difference( P < 0. 01). Conclusions Qingdu decoction can improve the function of liver by reducing permeability of intestinal mucosa of severe liver injury rats. The mechanism may be related to reduce harmful substances passing through intestinal mucosal barrier and enterohepatic circulation which can increase the incidences of hepatic injury.
Objective To observe the effect of Qingdu decoction on intestinal mucosal permeability in rats with severe liver injury,and to explore the mechanism of it to treat chronic severe hepatitis( CSH). Methods Severe liver injury model was establish by thioacetamide( TAA),and Qingdu decoction was used to treat them,then blood biochemical method,ELISA,Western Blot was used to observe theeffect of total bilirubin( TBIL),aspartate aminotransferase( AST) which reflect liver function,and diamine oxidase( DAO),blocking binding protein-1( ZO-1) and interleukin of intestinal tissue( IL-1,IL-6) which reflect intestinal mucosal permeability of this model rats. Results( 1) Compared with the model group,the level of TBIL,AST,DAO in the lactulose group,the low and medium dose groups of Qingdu decoction were significantly decreased( P < 0. 01); the expression level of ZO-1 protein in all treatment groups were significantly increased( P < 0. 01); the level of IL-1β and IL-6 in lactulose group and the Qingdu decoction medium dose group were significantly decreased( P < 0. 01);( 2) Compared with the lactulose group,the level of TBIL,AST,DAO,IL-1β in the Qingdu decoction medium dose group was decreased obviously( P< 0. 05),the expression level of ZO-1 was increased significantly( P < 0. 01); IL-6 in the Qingdu decoction low dose group was decreased obviously( P < 0. 05); AST,DAO in the Qingdu decoction high dose group had significantly statistical difference( P < 0. 01). Conclusions Qingdu decoction can improve the function of liver by reducing permeability of intestinal mucosa of severe liver injury rats. The mechanism may be related to reduce harmful substances passing through intestinal mucosal barrier and enterohepatic circulation which can increase the incidences of hepatic injury.
引文
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[5]高连印,车念聪,王融冰,等.清毒汤对TAA致肠源性内毒素血症大鼠肝脏库普弗细胞CD14和清道夫受体表达的影响[J].北京中医药,2011,30(12):947-948.
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[7]Norman K,Pirlich M.Gastrointestinal tract in liver disease:which organ is sick[J].Curr Opin Clin Nutr Metab Care,2008,11(5):613-619.
[8]刘玉凤.DSS所致的慢性实验性结肠炎加重CCl4诱导的肝纤维化及其机制研究[D].石家庄:河北医科大学,2014.
[9]林睿.肠黏膜屏障损伤对自身免疫性肝炎患者枯否细胞免疫调节功能影响的研究[D].天津:天津医科大学,2013.
[10]罗佳佳,曹吴冰,高连印.重型肝炎肠源性内毒素血症的中医药治法初探[J].继续医学教育,2015,29(12):155-156.
[2]宋怀宇,姜春华,杨建荣,等.重度慢性乙型肝炎患者肠黏膜通透性的变化及相关因素分析[J].山东医药,2010,50(25):27-28.
[3]Loguercio C,De Simone T,Federico A,et al.Gut-liver axis:a new point of attack to treat chronic liver damage?[J].Am J Gastroenterol,2002,97(8):2144-2146.
[4]王融冰,刘军民,吴云忠,等.清毒汤治疗肝病肠源性内毒素症临床观察[J].中西医结合肝病杂志,2004,14(3):135-137.
[5]高连印,车念聪,王融冰,等.清毒汤对TAA致肠源性内毒素血症大鼠肝脏库普弗细胞CD14和清道夫受体表达的影响[J].北京中医药,2011,30(12):947-948.
[6]Nolan JP.The role of intestinal endotoxin in liver injury:a long and evolvinghistory[J].Hepatology,2010,52(5):1829-1835.
[7]Norman K,Pirlich M.Gastrointestinal tract in liver disease:which organ is sick[J].Curr Opin Clin Nutr Metab Care,2008,11(5):613-619.
[8]刘玉凤.DSS所致的慢性实验性结肠炎加重CCl4诱导的肝纤维化及其机制研究[D].石家庄:河北医科大学,2014.
[9]林睿.肠黏膜屏障损伤对自身免疫性肝炎患者枯否细胞免疫调节功能影响的研究[D].天津:天津医科大学,2013.
[10]罗佳佳,曹吴冰,高连印.重型肝炎肠源性内毒素血症的中医药治法初探[J].继续医学教育,2015,29(12):155-156.