丹参注射液抑制4-羟基壬烯醛预防酒精性肝病的机制研究  

Danshen Injection Prevent Alcoholic Liver Disease via Decreasing Level of 4-hydroxynonenal

作　　者：张福利[1] 丁蕾[1] 马旺[1] 胡林峰[1] 朱林文思 唐利华[1] 夏永良[3] 窦晓兵[1] 

机构地区：[1]浙江中医药大学生命科学学院,杭州310053 [2]上海交通大学医学院 [3]浙江中医药大学第一临床医学院

出　　处：《浙江中医药大学学报》2016年第8期579-584,共6页Journal of Zhejiang Chinese Medical University

基　　金：国家自然基金面上项目(81473393)~~

摘　　要：[目的]利用C57BL/6小鼠建立小鼠酒精性肝病(alcoholic liver disease,ALD)模型,明确丹参注射液通过抑制肝细胞内4-羟基壬烯醛(4-hydroxynonenal,4-HNE)产生预防ALD的作用,并阐明其抑制4-HNE产生的作用机制。[方法]根据Lieber-De Carli方法进行小鼠ALD造模,并用丹参注射液进行药物干预,利用HE染色、酶联免疫法等技术检测小鼠肝脏病理、血清谷丙转氨酶(alanine aminotransferase,ALT)、肝脏甘油三酯(triglyceride,TG)等水平变化,利用Western Blot等技术分析肝组织内过氧化物增殖激活受体α(peroxisome proliferator activated receptors,PPARα)、核转录因子kappa B(nuclear factor-кB,NF-κB)蛋白水平及4-HNE与蛋白质加合物的变化。[结果]1ALD小鼠模型成功建立。2丹参注射液可降低血清ALT、肝脏TG的水平,差异有统计学意义(P<0.01),病理学结果表明丹参注射液可显著减少小鼠肝细胞内的脂肪变性。3丹参注射液能使小鼠肝内4-HNE与蛋白质形成的加合物降低,PPARα蛋白、NF-κB蛋白表达水平增加,差异有统计学意义(P<0.01)。[结论]丹参注射液能通过激活肝脏内的PPARα信号通路,抑制肝脏内的4-HNE产生,并激活NF-κB介导的抗凋亡通路,预防ALD。[Objective] The effect of Danshen Injection on the inhibition of 4-Hydroxynonenal in a mouse model of alcoholic liver disease（ALD）.[Metheds] Mice were fed ethanol-containing Lieber-DeCarli diet and injected Danshen.The levels of ALT and TG were measured by HE and relative kits. The expression of 4-hydroxynonenal（4-HNE）, peroxisome proliferator activated reeeptors（PPARct）, NF-κB in the liver was determined by Western Blot, respectively. [Resultes] （1）Mice ALD model was built successfully. （2）Danshen injection significantly reduced the level of ALT,TG（P〈0.01） and inhibited hepatic lipid accumulation. （3）Compared with the Control Group, the expression of 4-HNE level and protein of the liver was significantly increased in ALD Group（P〈0.01）. Danshen Injection inhibited 4-HNE and activated PPARα and NF-κB （p65）. [Conclusion] Supplementation of Danshen Injection, conferred a protective effect on ALD in mice, was associated with active hepatic PPARα, and decreased hepatic 4-HNE accumulation, and improved hepatic NF-KB activity.

关 键 词：ALD 丹参注射液 4-HNE PPARΑ NF-κB 预防 

分 类 号：R331[医药卫生—人体生理学]