埃克替尼对二甲基亚硝胺诱导肝纤维化大鼠的作用

发布时间：2019-01-05 21:12

【摘要】：目的观察埃克替尼对二甲基亚硝胺(DMN)大鼠实验性肝纤维化的影响。方法 48只雄性Wistar大鼠随机分为正常组(n=10)、模型组(n=14)、扶正化瘀组(n=12)与埃克替尼组(n=12)。模型组、扶正化瘀组和埃克替尼组以DMN 10μg·kg-1体重腹腔注射复制肝纤维化模型,每周连续3 d,连续4周;首次注射剂量为正常剂量2/3。自造模第3周开始,扶正化瘀组与埃克替尼组分别给予扶正化瘀胶囊4.0 g·kg-1、埃克替尼5 mg·kg-1灌胃,每周连续7 d,连续4周。HE染色与胶原染色观察肝组织炎症与胶原沉积,试剂盒检测血清肝功能水平,Jamall法测定肝组织羟脯氨酸(HYP)含量。荧光定量PCR检测肝组织α-平滑肌肌动蛋白(α-SMA)与转化生长因子-β(TGF-β)表达。结果与正常组相比,模型组大鼠的腹水发生率、血清总胆红素(T.Bil)含量、丙氨酸转氨酶(ALT)与天冬氨酸转氨酶(AST)活性、肝组织HYP含量均明显升高(P0.01),血清白蛋白(Alb)含量明显减少,肝组织炎症及胶原沉积加重(P0.01),肝组织α-SMA及TGF-βm RNA表达增多(P0.05)。埃克替尼可明显减少造模大鼠腹水发生率,降低ALT、AST、T.Bil水平和肝组织HYP(P0.05),减轻肝组织炎症及胶原沉积(P0.05),下调肝组织α-SMA及TGF-βm RNA表达(P0.05)。结论埃克替尼能够改善DMN诱导的大鼠实验性肝纤维化。
[Abstract]:Objective to observe the effect of ectini on experimental hepatic fibrosis in rats with dimethylnitrosamine (DMN). Methods 48 male Wistar rats were randomly divided into normal group (n = 10), model group (n = 14), control group (n = 12) and Eketinib group (n = 12). Model group, Fuzheng Huayu group and Eketinib group were injected intraperitoneally with DMN 10 渭 g kg-1 for 3 days a week for 4 weeks. Since the 3rd week of model making, Fuzheng Huayu group and Eketinib group were given 4. 0 g kg-1, Eketini 5 mg kg-1 by gavage, 7 days a week, respectively, in Fuzheng Huayu group and Eketini group. HE staining and collagen staining were used to observe liver inflammation and collagen deposition. Serum liver function and hydroxyproline (HYP) were detected by Jamall method. The expression of 伪-smooth muscle actin (伪-SMA) and transforming growth factor-尾 (TGF- 尾) in liver tissue was detected by fluorescence quantitative PCR. Results the incidence of ascites, the content of serum total bilirubin (T.Bil), the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and the content of HYP in liver tissue in the model group were significantly higher than those in the normal group (P0.01). The content of serum albumin (Alb) decreased significantly, the inflammation of liver tissue and collagen deposition aggravated (P0.01), and the expression of 伪-SMA and TGF- 尾 m RNA in liver tissue increased (P0.05). Eketinine significantly reduced the incidence of ascites, decreased the level of ALT,AST,T.Bil and HYP in liver tissue (P0.05), and alleviated inflammation and collagen deposition in liver tissue (P0.05). The expression of 伪-SMA and TGF- 尾 m RNA in liver tissue was down-regulated (P0.05). Conclusion Eketinib can improve experimental hepatic fibrosis induced by DMN in rats.
【作者单位】：上海中医药大学附属曙光医院肝病研究所;上海高校中医内科学E-研究院;上海市中医临床重点实验室;肝肾疾病病证教育部重点实验室;
【基金】：国家科技重大专项(2014ZX10005001) 上海市医学领军人才计划(LJ10005)
【分类号】：R575.2

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