转化生长因子-β_1和Smad7信号通路与大鼠肝纤维化的相关性

Relationship of transforming growth factor-β_1 and Smad7 signal pathway with hepatic fibrosis in rats

目的探讨肝纤维化组织中转化生长因子-β1(transforming growth factor-β1,TGF-β1)、Smad7基因在信号传导通路中的作用。方法 40只Wistar大鼠随机分为对照组和模型组各20只,模型组腹腔注射质量分数10%四氯化碳注射液8周,对照组腹腔注射质量分数0.9%氯化钠注射液。2组于8周后检测血清谷草转氨酶(glutamic-pyruvic transaminase,GPT)、透明质酸(hyaluronic acid,HA)和TGF-β1水平,组织病理观察肝组织炎症反应及纤维化程度,采用Western blot与RT-PCR法检测肝组织TGF-β1、Smad3、Smad7蛋白和mRNA水平。结果模型组血清GPT[(178.45±24.36)u/L]、HA[(693.37±206.35)μg/L]和TGF-β1[73.94±28.37)u/L]水平明显高于对照组[(42.80±8.37)u/L、(59.35±28.12)μg/L和(20.68±17.85)u/L](P<0.05);模型组肝组织TGF-β1mRNA和蛋白(0.86±0.04、3.86±0.87)、Smad3mRNA和蛋白(0.52±0.03、2.63±0.94)表达水平高于对照组(0.31±0.03、1.07±0.60,0.21±0.01、0.81±0.04)(P<0.05),Smad7 mRNA和蛋白(0.33±0.02、1.20±0.53)表达水平低于对照组(0.77±0.02、2.83±1.15)(P<0.05)。结论 TGF-β1、Smad7信号传导通路过度活化及血清GPT、HA和TGF-β1水平升高,可能与肝纤维化的发生和发展密切相关,TGF-β1高表达在促进肝纤维化发生中起重要作用。

Objective To explore the role of transforming growth factor-βl （TGFβ1） in liver fibrosis organization and Smad7 gene role in signal transduction pathways in hepatic fibrosis. Methods Forty Wistar rats were randomly divided into control group and model group, with 20 rats in each group. Model group received intraperitoneal injection of 10% CCl4 for 8 weeks, and control group received intraperitoneal injection of 0. 9% sodium chloride. The serum glutamic pyruvic transaminase （GPT）, hyaluronic acid （HA） and TGF-β1 levels were detected 8 weeks later in both groups. HE staining was used to observe the liver tissue inflammatory reaction and fibrosis degree, and Western blot and rt-PCR method were used to detect TGF-β1 , and Smad3 and Smad7 protein and mRNA levels in liver tissue. Results The serum GPT, HA and TGF-β1 were significantly higher in model group （（178. 45 ± 24.36） u/L, （693. 37 ± 206. 35） μg/L）, （73.94±28.37） μ/L） than those in control group （（42.80±8.37） u/L, （59.35±28.12） μg/L, （20.68±17.85）μ/L） （P〈0.05）. TGF-β1 mRNA and protein （0.86±0.04, 3. 86±0. 87）, and Smad3 mRNA and protein （0. 52±0.03, 2.63±0.94） levels were significantly higher in model group than those in control group （0. 31±0.03, 1.07±0. 60; 0.21±0.01, 0.81±0.04） （P〈 0.05）, and Smad7 mRNA and protein levels were significantly lower in model group （0.33± 0.02, 1.20± 0. 53） than those in control group （ 0. 77 ± 0.02, 2. 83±1. 15 ） （ P〈 0.05）. Conclusion The excessive activation of TGF-β1 and Smad7 signaling pathways and elevated levels of serum GPT, HA and TGF-β1 may be closely correlated with the development and progression of liver fibrosis, and the high expression of TGF-β1 plays an important role in promoting liver fibrosis.