生长抑制因子AcSDKP对转化生长因子β1促活化肝星状细胞合成和分泌细胞外基质的影响  

Effects of AcSDKP on Synthesis and Secretion of Extracellular Matrix in Hepatic Stellate Cells Mediated by TGF-β1

作　　者：刘博伟[1] 于静[1] 陈源文[2] 李定国[2] 兰玲[1] 袁媛[1] 贾长河[1] 张昊[1] 

机构地区：[1]河南省人民医院老年医学部消化科,郑州450003 [2]上海交通大学医学院附属新华医院消化内科,上海200092

出　　处：《中国药房》2012年第5期408-411,共4页China Pharmacy

摘　　要：目的:观察生长抑制因子N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸(AcSDKP)对转化生长因子β(1TGF-β1)促活化肝星状细胞(HSC)合成和分泌细胞外基质(ECM)的影响,探讨其抗纤维化作用机制。方法:大鼠HSC经原代分离培养活化后,分为空白对照组、TGF-β1组(5μg.L-1)、AcSDKP组(1nmol.L-1)、混合处理组(AcSDKP1nmol.L-1+TGF-β15μg.L-1),每组6个复孔,加入相应药物培养72h后,观察各组HSC形态学变化,检测其中Ⅰ型胶原(ColⅠ)mRNA、α平滑肌肌动蛋白(α-SMA)蛋白的表达及HSC上清液中玻璃酸(HA)的含量。结果:与空白对照组比较,TGF-β1组HSCColⅠmRNA表达、HA含量均明显升高(P<0.05),AcSDKP组ColⅠmRNA表达、HA含量、α-SMA蛋白表达均明显降低(P<0.05);与TGF-β1组比较,混合处理组ColⅠmRNA表达、HA含量、α-SMA蛋白表达均明显降低(P<0.05)。结论:AcSDKP可能通过抑制TGF-β1介导的活化HSC合成和分泌ECM,从而发挥其抗肝纤维化作用。OBJECTIVE： To observe the effect of growth inhibitory factor N-acetyl-seryl-aspartyl-lysyl-proline （AcSDKP） on synthesis and secretion of extracellular matrix in hepatic stellate cells （HSC） mediated by transforming growth factor β1 （TGF-β1）, and to explore anti-fibrotic effect. METHODS： Primary cultures of HSC were subjected to different treatment when they were activated, that is blank control group, TGF-β1 group （5μg·L-1）, AcSDKP group （1 nmol L-1） and mixed treatment group （AcSDKP 1 nmol L ＋TGF-β1 5μg·L-1） with 6 wells in each group. Those groups were given relevant medicine and cultured for 72 h. The morphological changes of HSC were observed. Hyaluronic acid （HA） in the supernatant was determined, and the expressions of collagen I （Col I ） mRNA and α-SMA were measured. RESULTS： Compared with blank control group, the expression of Col [ mRNA and HA content in TGF-β1 group increased significantly （P〈0.05）, and the expression of Col I mRNA and u-SMA protein, HA content decreased significantly in AcSDKP group （P〈0.05） ; compared with TGF-β1 group, the expression of Col I mRNA and α-SMA protein, HA content decreased significantly in mixed treatment group （P〈0.05）. CONCLUSION： AcSDKP inhibits synthesis and secretion of extracellular matrix mediated by TGF-β1 in rat HSC, and mechanism of which is possibly related with the anti-fibrosis effect of AcSDKP.

关 键 词：N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸 肝星状细胞 转化生长因子Β1 细胞外基质 

分 类 号：R575.2[医药卫生—消化系统]