糖尿病大鼠肝脏核因子-κB、转化生长因子β1、纤维连接蛋白的表达与肝纤维化的关系  

The relationship between the expression of NF-κB, TGFβ1, FN and hepatic fibrosis in diabetic rats

作　　者：王蓉蓉[1] 陈祥义[1] 廖鸿力[1] 万丽[1] 李剑敏[1] 陈丽玲[2] 陈筱菲[2] 陈国荣[1] 

机构地区：[1]浙江省温州医学院附属第一医院病理科,325000 [2]浙江省温州医学院附属第一医院检验科,325000

出　　处：《中华肝脏病杂志》2010年第3期194-198,共5页Chinese Journal of Hepatology

基　　金：浙江省科技攻关项目（2007C34003）;温州医学院重大项目（XNK05010）

摘　　要：目的观察糖尿病大鼠肝组织核因子（NF）-κB、转化生长因子（TGF）β1、纤维连接蛋白（FN）mRNA蛋白的表达，探讨其在糖尿病性肝纤维化发生中的作用。方法远交群大鼠20只，随机分为正常对照组10只，2型糖尿病组10只。2型糖尿病组在喂以高脂饮食4周后，注射30mg／kg链脲佐菌素诱导2型糖尿病大鼠模型，继续给予高脂饮食12周。光镜下观察肝脏纤维化病变，RT-PCR法检测肝组织NFKB、TGFβ1、FNmRNA的表达，免疫组织化学法检测肝组织NF—KB、TGFβ1、FN的蛋白表达。用SPSS11．5统计软件进行统计学分析，采用t检验或秩和检验和Spearman秩相关分析。结果2型糖尿病组大鼠肝组织出现不同程度的肝纤维化病变。2型糖尿病组大鼠肝组织TGFβ1和FN基因mRNA的相对表达量分别为0．91±0．19和1．85±0．70，正常组分别为0．47±0．20和1．22±0．39，两组比较，t值分别为-5．233和-2．463，P值均〈0．05，差异均有统计学意义。2型糖尿病组大鼠肝组织NF-κBP65、TGFD1的表达量分别为10978．77±8782．59和8551．00±4768．68，正常组分别为4206．86±1430．56和4036．85±1051．12，两组比较，z值分别为-1．979，-2．303，P值均〈0．05，差异均有统计学意义。FN蛋白表达量在2型糖尿病组为16980。30±11529．29，正常组为5701．95±9461．75，两组比较，f=2．391，P〈0．05，差异有统计学意义。结论糖尿病大鼠肝组织NF-κB、TGFβ1、FN表达的增强及NF-κB活性的增强可能是糖尿病大鼠肝纤维化的重要机制之一。Objective To investigate the expression of nuclear factor kappa B （NF-κB）, transforming growth factor β1 （TGF β1）, fibronectin （FN） in liver from diabetic rats. Methods Twenty male Sprague-Dawley rats were divided randomly into two groups： normal control group （n = 10） and type 2 diabetic group （n = 10）. After 4 weeks of high-fat feeding, diabetic group rats were injected with low dosage strepozotocin （30 mg/kg） intraperitoneally to induce type 2 diabetic rat models. The diabetic rats recieved high-fat feeding for another 12 weeks. At the end of the experiment, the fibrosis lesion was observed under light microscopy after Masson staining. The mRNA levels of NF-κB, TGF β1, FN from rats liver wereassayed by semi-quantity RT-PCR, the protein levels of NF-κ B, TGF β 1, FN was detected by IHC. Results Fibrosis was found in diabetic rats. The levels of TGFβ1, FN mRNA in liver tissues increased in diabetic rats compared with normal control rats （0.91 ± 0.19 vs 0.47 ± 0.20, t = 5.233, P 〈 0.05; 1.85 ± 0.70 vs 1.22 ± 0.39, t = 2.463, P 〈 0.05）. And the protein levels of NF-κB P65, TGF B 1, FN in liver tissues from diabetic rats were significantly higher than those in normal control rats （10978.77 ± 8782.59 vs 4206.86 ± 1430.56, Z= 1.979, P 〈 0.05; 8551.00 ± 4768.68 vs 4036.85 ± 1051.12, Z= 2.303, P〈 0.05; 16980.30 ± 11529.29 vs 5701.95 ± 9461.75, t = -2.391, P 〈 0.05）. Conclusion Upregulation of NF-κB, TGF β1, FN in liver tissues may play a role in the hepatic fibrogenesis in diabetic rats.

关 键 词：大鼠 糖尿病 肝硬化 相关性分析 

分 类 号：R587.2[医药卫生—内分泌] R575.2[医药卫生—内科学]