论文部分内容阅读
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(P<0.01),血清白蛋白(Alb)含量明显减少,肝组织炎症及胶原沉积加重(P<0.01),肝组织α-SMA及TGF-βm RNA表达增多(P<0.05)。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(P<0.05),减轻肝组织炎症及胶原沉积(P<0.05),下调肝组织α-SMA及TGF-βm RNA表达(P<0.05)。结论埃克替尼能够改善DMN诱导的大鼠实验性肝纤维化。
Objective To investigate the effect of icotinib on experimental hepatic fibrosis in dimethylnitrosamine (DMN) rats. Methods Forty eight male Wistar rats were randomly divided into normal group (n = 10), model group (n = 14), Fuzhenghuayu group (n = 12) and icotinib group (n = 12). The model group, Fuzheng Huayu group and Icitinib group were given intraperitoneal injection of DMN 10 μg · kg -1 to replicate the model of hepatic fibrosis for 3 consecutive days every week for 4 weeks. The initial injection dose was 2/3 of the normal dose. Starting from the third week of modeling, Fuzhenghuayu and Icitinib groups were treated with Fuzhenghuayu Capsule 4.0 g · kg-1 and Icitinib 5 mg · kg-1, respectively, for 7 days a week, For 4 weeks. Hepatic inflammation and collagen deposition were observed by HE staining and collagen staining. Serum levels of liver function were detected by kit. Hydroxyproline (HYP) content of liver tissue was measured by Jamall method. Fluorescent quantitative PCR was used to detect the expression of α-smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β) in liver tissue. Results Compared with the normal group, the incidence of ascites, the content of total bilirubin, the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the level of HYP in liver tissue (P <0.01), serum albumin (Alb), hepatic inflammation and deposition of collagen increased significantly (P <0.01), and the expression of α-SMA and TGF- . Icitinib could significantly reduce the incidence of ascites in rats and decrease the levels of ALT, AST, T.Bil and HYP in liver tissue (P <0.05), and alleviate liver inflammation and collagen deposition (P <0.05) α-SMA and TGF-βm RNA (P <0.05). Conclusion Icitinib can improve DMN-induced experimental hepatic fibrosis in rats.