硼替佐米对大鼠肝纤维化动物模型NF-κB和TGF-β1表达的调控  

Bortezomib regulates NF-κB and TGF-β1 expression in hepatic fibrosis in a rat model

作　　者：潘雯[1] 陈旭平[1] 苏松[2] 陶中桦 

机构地区：[1]成都市第六人民医院消化内科,四川省成都市610051 [2]泸州医学院附属医院肝胆外科,四川省泸州市646000 [3]泸州医学院基础医学研究中心,四川省泸州市646000

出　　处：《世界华人消化杂志》2015年第6期894-900,共7页World Chinese Journal of Digestology

基　　金：2011年四川省卫生厅科研基金资助项目;No.110051~~

摘　　要：目的:研究蛋白酶体抑制剂硼替佐米(bortezomib,Bor)对大鼠肝纤维化动物模型肝纤维化肝细胞损害的保护作用,并探讨其保护机制.方法:将30只SD大鼠随机分为正常饮食组(normal diet group,ND组)、肝纤维化对照组(liver fibrosis group,LF组)和Bortezomib干预组(bortezomib group,Bor组),每组处死大鼠后收集肝脏标本,分别进行HE和Masson染色了解肝纤维化水平、p65免疫组织化学染色检测核因子κB(nuclear factor-kappa B,NFκB)活性、实时定量PCR检测转化生长因子β1(transforming growth factorβ1,TGF-β1m RNA水平、Western blot检测TGF-β1蛋白表达.结果:HE和Masson染色发现Bor组的肝纤维化水平较LF组低;Bor组的NF-κB p65亚基阳性染色率(4.72±1.20)明显低于LF组(9.05±1.33)(P<0.05);实时定量PCR显示Bor组TGF-β1 m RNA相对表达量(0.96±0.23)明显低于LF组(1.64±0.26)(P<0.05);Western blo检测结果显示Bor组(1.34±0.06)明显低于LF组(1.72±0.14)(P<0.05).结论:Bor可以通过下调TGF-β1表达、降低核因子NF-κB的活性,减少肝细胞凋亡的发生,减轻肝纤维化程度,从而降低肝纤维化造成的肝细胞损害程度.AIM： To assess the protective effect of the proteasomeinhibitor bortezomib on liver fibrosis in rats and to explore the possible mechanism. METHODS： Thirty SD rats were randomized into three groups： a normal diet group （ND group）, a liver fibrosis group （LF group） and a bortezomib group （Bor group）. After treatment, the rats in each group were sacrificed. Hepatic fibrosis was assessed by HE and Masson trichrome staining. The expression of nuclear factor-kappa B （NF- KB） p65 was assessed by irnmunohistochemistry. Real-time PCR was employed to detect the transforming growth factor [31 （TGF-β1） mRNA level in liver samples. The expression of TGFq31 protein was determined by Western blot analysis. RESULTS： The hepatic fibrosis level in the Bor group was significantly lower than that in the LF group as revealed by HE and Masson staining. The positive rate of NF-kB p65 subunit was significantly lower in the Bor group than in the LF group （4.72 vs 9.05, P 〈 0.05）. The expression of TGF-β1 mRNA was significantly lower in the Bor group than in the LF group （0.96 vs 1.64, P 〈 0.05）. The expression of TGF-β1 protein was also significantly lower in the Bor group than in the LF group （1.34 vs 1.72, P 〈 0.05）. CONCLUSION： These findings suggest that bortezomib reduces hepatocyte injury in rats with hepatic fibrosis possibly by suppression of NF-~：B activation and TGF-β1 expression.

关 键 词：硼替佐米 肝纤维化 核因子ΚB 转化生长因子Β1 

分 类 号：R965[医药卫生—药理学]