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.
出处
《世界华人消化杂志》
CAS
北大核心
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~~
