丹参酮ⅡA对小鼠肝纤维化的干预作用

作者	单位
孙瑞芳	山西医科大学第一临床医学院
刘立新	山西医科大学第一临床医学院
张海燕	山西医科大学第一临床医学院
张骞骞	山西医科大学第一临床医学院

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中文摘要:

目的通过观察胰岛素样生长因子结合蛋白7(IGFBP7)、转化生长因子-β1(TGF-β1)/Smad3信号通路在丹参酮ⅡA作用的肝纤维化小鼠肝组织中的作用,探讨丹参酮ⅡA护肝作用的新机制。方法腹腔注射硫代乙酰胺(TAA)制备肝纤维化模型。将36只雄性昆明小鼠随机分为5组:正常对照组、4周模型组、4周预防组、6周模型组、3周治疗组。检测血清丙氨酸氨基转氨酶(ALT)和乳酸脱氢酶(LDH)活力,进行HE和Masson染色观察肝组织形态学变化,免疫组织化学染色检测α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原(collagenⅠ)、纤维粘连蛋白(FN)、TGF-β1、Smad3和IGFBP7的表达;用TUNEL方法检测肝细胞凋亡;Westernblot检测肝组织FN、Smad3和IGFBP7的含量。结果分别与4周和6周模型组比较,4周预防组和3周治疗组血清ALT、LDH含量明显降低,肝组织损伤显著改善,肝细胞凋亡指数降低;肝组织α-SMA、collagenⅠ、FN、TGF-β1、Smad3和IGFBP7的表达亦明显减少;肝组织FN、IGFBP7和Smad3含量减少,各组比较差异有统计学意义(P<0·05)。结论丹参酮ⅡA具有改善肝功能、抑制肝星状细胞活化、减少细胞外基质(ECM)生成、保护肝细胞的作用,其机制可能与阻止TGF-β1/Smad3信号通路,降低肝组织IGFBP7的表达有关。

英文摘要:

Objective To explore the mechanism of action of tanshinoneⅡA for liver protection in hepatic fibrotic mice by observing its effects on signaling pathway of insulin-like growth factor binding protein 7 (IGFBP7) and TGFβ1/Smad3.Methods Hepatic fibrosis model was induced by intraperitoneal injection of thiacetamide (TAA).Thirty-six male Kunming mice were divided into five groups:the normal control group (N),the 4-week model group (A),the 4-week tanshinoneⅡA prevented group (B),the 6-week model group (C) and the 3-week tanshinoneⅡA treated group (D).Changes of serum levels of alanine aminotransferase (ALT) and lactate dehydrogenase (LDH),histopathology of liver (HE staining),area density of collagen in liver (Masson staining),expressions of α-smooth muscle actin (α-SMA),collagen Ⅰ,fibronectin (FN),transforming growth factor-β1 (TGF-β1),Smad3 and IGFBP7 in liver (by immunohistochemistry),liver content of FN,Smad3 and IGFBP7 (by Western blot),and the hepatocyte apoptosis (by TUNEL) were observed.Results The serum levels of ALT and LDH,the expressions of α-SMA,collagenⅠ,TGF-β1 in liver,expressions and contents of FN,Smad3 and IGFBP7 in liver were significantly lower;the liver damage and the hepatic apoptosis index were lesser in Group B than in Group A,also in Group D than in Group C,respectively,all showing statistical significance (P<0.05).Conclusion Tanshinone ⅡA could improve liver function,inhibit the activation of hepatic stellate cells,reduce the production of extracellular matrix,and protect the hepatocytes,and its of mechanisms of actions might be related with blocking TGF-β1/Smad3 signaling pathway and down-regulating the expression of IGFBP7 in liver.

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