水飞蓟素抑制大鼠酒精性脂肪肝库普弗细胞NF-κB活性的研究  

Protective effect of silymarin on alcoholic fatty liver in rats possibly via impairing NF-κB activation

作　　者：高学梅[1] 洪汝涛[1] 李俊[2] 胡奇珍 

机构地区：[1]安徽医科大学第一附属医院消化内科,安徽省消化疾病重点实验室,合肥230022 [2]安徽医科大学药学院,合肥230032

出　　处：《安徽医科大学学报》2014年第9期1242-1245,共4页Acta Universitatis Medicinalis Anhui

基　　金：安徽省年度科研计划项目(编号:10020503084)

摘　　要：目的探讨水飞蓟素抑制酒精性脂肪肝库普弗细胞(KCs)核转录因子-κB(NF-κB)活性及与酒精性脂肪肝的关系。方法 45只大鼠随机分为4组:正常组9只,模型组12只,水飞蓟素低、高剂量组各12只,采用酒精灌胃8周制造酒精性脂肪肝模型,HE染色观察肝脏病理组织学改变,联合酶离体灌注消化,Nycodenz密度梯度离心提取肝脏KCs,ELISA法检测其培养上清液白介素-6(IL-6)和细胞间黏附分子-1(ICAM-1)含量,RT-PCR法检测各组大鼠肝脏KCs NF-κB p65 mRNA表达。结果与正常组比较,模型组肝细胞可见明显脂肪变性,肝细胞肿胀明显(P<0.01)。与模型组比较,水飞蓟素各组肝组织病理变化程度均明显减轻(P<0.01)。ELISA法显示低、高剂量水飞蓟素组IL-6水平显著低于模型组(P<0.01),ICAM-1水平在低、高剂量组也低于模型组(P<0.05,P<0.01)。RT-PCR显示低、高剂量水飞蓟素组NF-κB p65 mRNA表达显著低于模型组(P<0.01)。结论水飞蓟素抑制肝脏KCs NF-κB及其基因产物的表达,提示水飞蓟素抑制酒精性脂肪肝进展可能与此有关。Objective To explore the inhibition of NF-κB activation by silymarin in kupffer ceils（KCs） in alcohol- ic fatty liver. Methods All rats were randomly divided into normal control group（n =9） ,model group（n = 12） and silymarin groups（ 100 mg/kg, 200 mg/kg; n = 12, respectively）. Rat model of alcoholic fatty livers were in- duced by intragastric infusion of ethanol for eight weeks. Histopathological changes of liver were assessed by hema- toxylin and eosin （HE） staining. Liver KCs were isolated by combined enzymatic digestion and isopyknic gradient centrifugation with nycodenz. The IL-6 and ICAM-1 contents of culture supernatants of KCs were detected by ELISA. NF-κB P65 mRNA expression of KCs was determined by RT-PCR. Results Compared with normal group, the liver cells of model group showed obvious steatosis and significant swelling（P 〈 0. 01 ）. Compared with model group, the degree of pathological changes in liver tissue in silymarin groups was significantly reduced （P 〈 0.01 ）. IL-6 levels in low and high dose of silymarin groups were significantly lower than those of model group （ P 〈 O. O1 ）. ICAM-1 levels in low and high dose of silymarin groups were also lower than those of model group（P 〈 0. 05, P 〈 0. 01 ）. NF-κB P65 mRNA expression in low and high dose of silymarin groups was significantly lower than those of model group（P 〈 O. 01 ）. Conclusion Silymarin inhibits NF-κB activation and its gene products, and it may hin- der the development of alcoholic fatty liver.

关 键 词：核转录因子KB 水飞蓟素 脂肪肝 酒精性 细胞间黏附分子-1 白介素-6 

分 类 号：R575.1[医药卫生—消化系统]