摘要
目的:观察实验性大鼠肝硬化形成过程中,肝组织TGF-β1,Smad3,Smad7水平的动态变化,研究三者在肝硬化发生过程中的作用及机制.方法:以SD大鼠为实验对象,于实验开始时处死6只大鼠作为wk 0正常对照组,剩余大鼠,600 mL/L四氯化碳3 mL/kg,sc,2次/ wk,复制肝硬化动物模型.于wk 3,6,9,12各处死一批大鼠,用RT-PCR检测动物肝组织中TGF-β1,TGF-βRⅡ的mRNA表达水平,Western blot检测肝组织中Smad3,Smad7蛋白水平,免疫组织化学方法检测动物肝组织中TGF-β1的表达和定位.结果:正常肝组织中有少量TGF-β1,TGF-βRⅡ的mRNA表达.随着肝纤维化及肝硬化的形成,模型组wk 0,3,6,9,12,TGF-β1,TGF-βRⅡ和Smad3表达量分别逐渐递增(TGF-β1:0.19±0.12,0.29±1.02,0.89±0.23,0.98±0.77,1.7±1.00;TGF-βRⅡ:0.30±0.22,0.49±0.16,1.02±0.33,1.51±0.72,2.14±1.02;Smad3:0.44±0.24,0.84±0.69,1.10±0.16,1.40±0.12,1.75±1.05),Smad7表达量呈逐渐减少(1.35±0.12,1.09±0.78,1.14±0.31,1.11±0.91,0.74±1.21).正常肝组织TGF-β1可见少量表达,主要在中央静脉周围肝细胞中.随着肝纤维化及肝硬化的形成,TGF-β1表达增强(P<0.01).结论:随着肝硬化的形成,肝脏中TGF-β1,TGF-βRⅡ和Smad3表达增加,Smad7表达下降.
AIM: To observe changes in transforming growth factor (TGF)-β1, Smad3 and Smad7 during liver fibrosis, and to study their role hepatic tissue during the formation of experimental liver cirrhosis in rats. METHODS: Male rats were divided into control group and model group. Control: Six male rats were killed at the beginning of the experiment as the week 0 group. Model: The surplus rats was injected subcutaneously 600 mL/L CC14 in oil two times per week at the dosage of 3 mL/kg body weight. The rats were sacrificed after 3, 6, 9 and 12 wk. Expression of mRNA for TGF-β1 and TGF-β receptor Ⅱ (TGF-β R Ⅱ ) in rat liver was detected by reverse transcription-polymerase chain reaction (RT-PCR), and Smad3 and Smad7 were determined by Western blotting. Meanwhile, the level of TGF-β1was measuredby immunocytochemistry RESULTS: TGF-β1 mRNA, TGF-β RⅡ mRNA and Smad3 at 3, 6, 9 and 12 wk were expressed in low amounts in the normal liver tissue, and were increased after CC14 treatment, while Smad7 at the same point was decreased (TGF-β1, 0.19 ± 0.12, 0.29 ± 1.02, 0.89 ± 0.23, 0.98 ± 0.77, 1.7 ± 1.00; TGF-β R Ⅱ, 0.30 ± 0.22, 0.49 ± 0.16, 1.02 ± 0.33,1.51 ± 0.72, 2.14± 1.02; Smad3, 0.44 ± 0.24, 0.84 ±0.69, 1.10 ± 0.16, 1.40 ± 0.12, 1.75 ± 1.05; Smad7, 1.35± 0.12,1.09 ± 0.78, 1.14 ± 0.31, 1.11 ± 0.91, 0.74± 1.21). TGF-β1was expressed at a low level in the portal vein of the normal liver. It was up-regulated in rats after CC14 treatment (P 〈 0.01). CONCLUSION: During hepatic fibrosis induced by CC14 in rats, expression of TGF-β1, TGF-β R Ⅱ and Smad3 was increased, while Smad7 was decreased. The mechanism may be that TGF-β1 causes liver fibrosis by increasing Smad3 and decreasing Smad7.
出处
《世界华人消化杂志》
CAS
北大核心
2007年第30期3163-3167,共5页
World Chinese Journal of Digestology
基金
浙江省中医药管理局资助项目
No.2005C147~~