uPA基因转染骨髓源性肝干细胞移植对肝纤维化大鼠HSC活化的影响  

Effect of uPA gene-transfected bone marrow-derived liver stem cell transplantation on activation of hepatic stellate cells in rat liver fibrosis

作　　者：孙超[1] 汪保灿[1] 陈源文[1] 陈颖伟[1] 李定国[1] 

机构地区：[1]上海交通大学医学院附属新华医院消化内科,上海市200092

出　　处：《世界华人消化杂志》2008年第27期3031-3035,共5页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.30500236;上海市教委科研资助项目;No.05BZ49;上海市科委医学临床研究重点科技攻关资助项目;No.064119527;上海市教委优秀青年教师科研专项基金资助项目;No.18040~~

摘　　要：目的:探讨尿激酶型纤溶酶原激活物(uPA)基因修饰骨髓源性肝干细胞(BDLSC)移植对CCl4诱导的大鼠肝星状细胞(HSC)激活的影响.方法:大鼠sc400mL/LCCl4造模.36只大鼠随机分为4组:(1)正常组:sc等量橄榄油;(2)模型组;(3)BDLSC组;(4)BDLSC-uPA组,每组9只.各组大鼠于第8周处死,留取血清及肝组织.观察大鼠肝功能的变化;采用免疫组织化学法和Western blot法检测大鼠肝组织α-平滑肌肌动蛋白(α-SMA)蛋白表达变化.结果:与模型组和BDLSC组相比,BDLSC-uPA组大鼠血清丙氨酸转氨酶(ALT)和总胆红素(TBIL)水平均有不同程度的降低(86.5±9.7vs187.1±14.8,113.5±15.7;11.5±2.1vs26.3±3.7,17.9±2.8,均P<0.01),血清透明质酸(HA)和Ⅲ型前胶原(PCⅢ)水平明显降低(47.4±10.1vs148.5±22.4,97.6±14.4;18.9±4.4vs39.0±6.1,28.2±4.1,均P<0.01);肝组织α-SMA表达显著下调(0.0174±0.0048vs0.3404±0.0662,0.1080±0.0408,均P<0.01).结论:uPA基因修饰BDLSC移植能有效抑制CCl4诱导的大鼠肝纤维化,改善纤维化大鼠的肝功能,且抑制HSC的活化可能是其抑制肝纤维化的主要机制之一.AIM： To investigate the effects of urokinase type plasminogen activator （uPA） gene-modified bone marrow-derived stem cell （BDLSC） transplantation on activation of hepatic stellate cells （HSCs） in rats with CCl4-induced liver fibrosis.METHODS： Rat liver fibrosis model was in-duced by subcutaneous injection of 400 mL/L CCl4. Thirty-six rats were randomly divided into four groups of 9 rats, including control group which was injected subcutaneously with the same dose of olive oil, model group, BDLSC group and BDLSC-uPA group. All rats were sacrificed to harvest serum and liver tissues at the end of the eighth week. Liver function changes were observed; the expression changes of α-smooth muscle actin （α-SMA） proteins were determined using immunohistochemistry and Western blotting. RESULTS： In the BDLSC-uPA group, the serum levels of alanine aminotransferase （ALT） and to-tal bilirubin （TBIL） in varying degrees decreased （86.5 ± 9.7 vs 187.1 ± 14.8, 113.5 ± 15.7; 11.5 ± 2.1 vs 26.3 ± 3.7, 17.9 ± 2.8, all P 〈 0.01）, serum levels of hyaluronic acid （HA） and procollagen Ⅲ （PC Ⅲ） were much lower （47.4 ± 10.1 vs 148.5 ± 22.4, 97.6 ± 14.4; 18.9 ± 4.4 vs 39.0 ± 6.1, 28.2 ± 4.1, all P 〈 0.01）. The expression of α-SMA protein in liver was down-regulated, compared with those in the model group and BDLSC group （0.0174 ± 0.0048 vs 0.3404 ± 0.0662, 0.1080 ± 0.0408, all P 〈 0.01）. CONCLUSION： uPA gene-modified BDLSC transplantation suppresses CCl4–induced hepat-ic fibrosis and ameliorates liver functions in rats effectively. Inhibiting the activation of HSC may be one of the main mechanisms for inhabitation of rat liver fibrosis.

关 键 词：尿激酶型纤溶酶原激活物 骨髓源性肝干细胞 肝纤维化 肝星状细胞 Α-平滑肌肌动蛋白 

分 类 号：R575.2[医药卫生—消化系统]