栀子柏皮汤对α-萘异硫氰酸酯诱导的肝内胆汁淤积大鼠的保护作用  

Protective effect of Zhizi Bopi decoction on α-naphthylisothiocyanate induced intrahepatic cholestasis in rats

作　　者：曹璐[1] 李俊[1] 黄成[1] 韩静文[1] 

机构地区：[1]安徽医科大学药学院,合肥230032

出　　处：《安徽医科大学学报》2013年第3期257-262,共6页Acta Universitatis Medicinalis Anhui

基　　金：博士科研启动基金(编号:XJ201118);高等学校博士学科点专项科研基金(编号:20093420110002)

摘　　要：目的探讨栀子柏皮汤对α-萘异硫氰酸酯(ANIT)诱导的肝内胆汁淤积大鼠的保护作用及可能机制。方法实验组大鼠灌胃给予栀子柏皮汤7 d,第7天给药后4 h给ANIT造模。48 h后,测血清总胆红素(TBIL)含量、碱性磷酸酶(ALP)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、γ-谷氨酰转肽酶(GGT)活性及肝匀浆组织中丙二醛(MDA)、还原型谷胱甘肽(GSH)含量、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性。RT-PCR法及Western blot法检测胆汁代谢相关的转运体胆盐输出泵(BSEP)、钠-牛磺酸共转运体(NTCP)及氧化应激相关酶细胞色素CYP2E1的表达。结果栀子柏皮汤能够呈剂量依赖性的降低血清TBIL、ALP、ALT、AST、GGT及肝组织中MDA、GSH含量;提高肝组织中SOD、GSH-Px活性;增加肝组织中BSEP的表达,降低NTCP及CYP2E1的表达。结论栀子柏皮汤对ANIT诱导的肝内胆汁淤积大鼠具有保护作用,其作用机制可能与调控胆汁代谢相关转运体及抗氧化损伤有关。Objective To investigate the protective effects of Zhizi Bopi decoction on rats against α-naphthylisothiocyanaten （ANIT）induced liver injury with cholestasis and analyzed the possible mechanism. Methods ANIT was used to mimick the drug-induced liver injuery. 48 h after the ANIT treatment, serum of total bilirubin （TBIL）, alkaline phosphatase （ALP）, alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, γ- glutamyhranspeptidase （GGT）, liver specimens of superoxide dismutase （SOD）, malondialdehyde （MDA）, glutathione （GSH）, and glutathione peroxidase （GSH-Px） were measured. To further explore the molecular mechanisms, we measured the expression of the bile metabolism-related transporters： bile salt export pump （BSEP）, sodium-taurocholate cotrans-porting polypeptide （NTCP） and the enzyme related to oxidative stress： cytochrome P4502E1 （CYP2E1） in both mRNA and protein level. Results Zhizi Bopi decoction improved live history with reduced the serum levels of TBIL, ALP, ALT, AST, GGT. Furthermore, hepatic MDA activities and contents in liver tissue were significantly reduced, while SOD, GSH, GSH-Px activities, which had been suppressed by ANIT were significantly elevated in the groups pretreated with Zhizi Bopi decoction in a dose-dependent manmer. Additionally, Zhizi Bopi decoction was found to increase the expression of liver NTCP, and decrease the BSEP in ANIT-induced liver injury with cholestasis. CYP＇2E1 was decreased in accordance with the protein expression. Conclusion Zhizi Bopi decoction exerts protective effects against ANIT-induced liver injury. The mechanisms could be related to transshipment of bile metabolism-related transporters and anti-oxidative damage.

关 键 词：栀子柏皮汤 ANIT 胆汁酸相关转运体 CYP2E1 

分 类 号：R286[医药卫生—中药学] R965[医药卫生—中医学]