大黄素对实验性淤胆型肝炎的治疗作用及其机制  

Effect and mechanism of emodin on cholestatic hepatitis

作　　者：丁艳[1] 赵雷[2] 梅红[1] 彭罕鸣[1] 高源[1] 黄志华[3] 康世秀[1] 

机构地区：[1]华中科技大学同济医学院附属妇女儿童医疗保健中心消化科,武汉430016 [2]华中科技大学同济医学院附属协和医院感染科 [3]华中科技大学同济医学院附属同济医院儿科

出　　处：《中华肝脏病杂志》2009年第5期368-373,共6页Chinese Journal of Hepatology

基　　金：湖北省自然科学基金（2007ABA080）

摘　　要：目的探讨人黄素对淤胆型肝炎的治疗作用及其机制。方法SD大鼠分为5组：大黄素组、熊去氧胆酸组、地寨米忪组、模型组、正常对照组，除正常对照组外，其余4组均给予α异硫氰酸萘酯50mg／kg一次灌胃大鼠建立淤胆型肝炎动物模型，并给予相应的药物干预，造模后24、48、72h分别处死大鼠。免疫组织化学法检测肝组织中核因子κB表达。实时荧光定量PCR愉测肌组织中早期生K反应因子1、中性札细片岜趋化因子1、巨噬细胞炎症蛋白-2mRNA表达，Westernblot检测肝组织中细胞间黏附分子1蛋白表达。双抗体夹心酶联免疫吸附法俭测肝组织肿瘤坏死因子α、白细胞介素6含量，硫代巴比妥酸比色法、黄嘌呤氧化酶法技比包法分别检测肝组织中丙二醛、超氧化物歧化酶、髓过氧化物酶含量。结果（1）造模后24、48、72h，大黄素组血清总胆红素分别为（32．8±3．7）μmol／L、（61．0±16．4）μmol／L和（10．8±4．5）μmol／L；直接胆红素分别为（26．0±3．1）0μmol／L、（49．4±18．2）umol／L和（8．0±3．0）μmol／L；ALT分别为（313．7±49．8）U／L、（664．3±96．5）U／L和（200．3±60．3）U／L，均明显低于模型组，P值均〈0．01，差异有统计学意义。（2）造模后24、48h，大黄素组的核网千KBp65核表达阳性细胞百分率分别为24．1％和9．8％，模型组分别为48．3％和26．5％，P值均〈0．01，差异有统计学意义。（3）造模后24、48h，大黄素组的细胞因子诱导的中性粒细胞趋化因子1、L!噬细胞炎症蛋白2mRNA表达、细胞间黏附分子1蛋白表达、肿瘤坏死因子α、白细胞介素6含量均较模型组显著降低（P值均〈0．01）。结论 大黄素可显著改善实验性淤胆型肝炎大鼠的肝功能，其作用机制可能与抑制NF-κB信号通路有关。Objective To explore the therapeutic effect and mechanism of emodin on cholestatic hepatitis. Methods Rats were divided into 5 groups： 1 group was untreated, the other 4 groups were treated with alpha-naphthylisothiocyanate （ANIT）, ANIT and emodin, ANIT and ursodeoxycholic acid, or ANIT and dexamethasone, respectively. At 24 h, 48 h and 72 h after the treatment, NF-kappa B, early growth response factor- 1 （Egr- 1）, cytokine-induced neutrophil chemoattractant 1 （CINC- 1 ）, macrophage inflammatory protein 2 （MIP-2）, intercellular adhesion molecule l （ICAM-1）,tumor necrosis factor alpha （TNF alpha） and interleukin-6 （IL-6） were assayed by immunohistochemistry, real-time PCR, western-blot and ELISA. The level of malondialdehyde （MDA）, superoxide Dismutase（SOD） and myeloperoxidase （MPO） were assayed by thiobarbituric acid method, xanthine oxidase method and colorimetric method, respectively. Results （1） Compared to the controls, emodin had a notable effect on total bilirubin （TB）, direct bilirubin （DB）, alanine aminotransferase （ALT） at all time points （all P 〈 0.05）. Compared to ursodeoxycholic acid, emodin had a notable effect on TB and DB at 24 h after the treatments, however, after 48 h, emodin had a notable effect only on TB （all P 〈 0.05）. Compared to Dexamethasone, emodin had a notable effect on TB at 48h time point, and it had a notable effect on ALT at all time points （all P 〈 0.05）. （2） The nuclei NF-kappa B p65 staining was significantly increased at 24h and 48h after ANIT treatment （all P 〈 0.05）, and emodin treatment could block the increase （all P 〈 0.05）. （3） Egr-1 mRNA level was not affected by emodin treatment （P 〉 0.05）; levels of CINC-1, MIP-2 mRNA and ICAM-1 protein were significantly decreased after emodin treatment （all P 〈 0.05）. （4） The levels of TNF alpha and IL-6 were decreased after emodin treatment（all P 〈 0.05）. （5） The levels of MDA at all time points and MPO at 24 h,4

关 键 词：大黄素 胆汁淤积 肝炎 核因子ΚB 信号传导 

分 类 号：R285.5[医药卫生—中药学]