肝卵圆细胞分化过程中SDF-1/CXCR4生物轴的作用研究  

Crucial role of SDF-1/CXCR4 interaction in the differentiation of hepatic oval cells

作　　者：焦兴元[1] 曾三平[1] 黄晓明[1] 胡以则[1] 罗灿侨[2] 杜军[3] 吴金浪[4] 

机构地区：[1]广州医学院第二附属医院普通外科,510260 [2]中山大学医学院医学院病理学教研室 [3]中山大学药学院分子生物中心 [4]中山大学医学院电镜室

出　　处：《中华普通外科学文献（电子版）》2008年第3期16-19,30,共5页Chinese Archives of General Surgery(Electronic Edition)

基　　金：广东省自然科学基金资助项目(04004534);广东省医学科学基金资助(A2003312)

摘　　要：目的探讨肝卵圆细胞的激活、增殖和分化过程中基质细胞衍生因子(stromal cell-derived factor-1,SDF-1)及其受体(CXCR4)生物轴的作用机制。方法在三个对照组(2/3肝部分切除组;2/3肝部分切除组及AMD3100预处理组、2/3部分肝切除与二乙酰氨基芴和AMD3100预处理组)的参照下,用光镜与透射电镜观察观察雄性Wistar大鼠经2/3部分肝切除+二乙酰氨基芴预处理后不同时间(术后3,5,7,10,14,21d)肝卵圆细胞的数量、形态和分布变化,采用SP免疫组化法检测卵圆细胞CK18、CK19、AFP、CXCR4和SDF-1的表达,用RT-PCR方法测定SDF-1和CXCR4 mRNA表达水平。结果2-AAF/PH组术后3￣10d,CK18、CK19、AFP、ADF-1和CXCR4表达阳性的细胞数量逐渐增加,CXCR4和SDF-1阳性表达见于汇管区附近肝小叶内增生的终末小胆管上皮细胞,以及与增生的胆管/终末小胆管在位置上相延续且形态相类似的卵圆细胞;术后10￣14d,CK18、CK19、AFP、ADF-1和CXCR4阳性细胞数达到最高值;之后,开始下降,至21d则下降至最低水平。自术后3d起,SDF-1和CXCR4mRNA表达水平同步升高,10d升高至峰值,较术后3,5,7d差异均有统计学意义(P均<0.01),之后开始下降,至21d则下降到最低水平。结论SDF-1/CXCR4生物轴可能有刺激肝干细胞的活化和促进肝卵圆细胞的增殖作用,趋化因子SDF-1及其受体CXCR4可能是肝卵圆细胞的重要标志物。Objective To investigate the mechanism of SDF-1/CXCR4 biological axis in the activation, proliferation and differentiation of hepatic oval cell. Methods Compared with three control groups （two-thirds hepatectomy. Two-thirds hepatectomy with AMD3100, two-thirds hepatectomy with 2-acetylaminoflunzene and AMD3100）, the pathological changes of oval cells of experiment group （two-thirds hepatectomy with 2-acetylaminoflunzene） were observed by light and transmission electron microscope in the different period （3,5,7,10,14,21 days after surgery）. CK18,CK19,AFP, SDF-1 and CXCR4 protein were continuously detected by immuno-histochemistry stainging, SDF-1 mRNA and CXCR4 mRNA were measured by RT-PCR. Results In the AAF/PH model, from 3 to 10 days after surgery, CK18, CK19,AFP, SDF-1 and CXCR4 protein expression positive cells progressively increased with time.SDF-1 and CXCR4 expressed on biliary cells lining interlobour bile ducts and oval cells which adjectent to proliferent bile duct cells. From 10 to 14 days after surgery, CK18,CK19, AFP, SDF-1 and CXCR4 protein expression positive cells increased to reach a maximal intensity and decreased thereafter, which decreased to reach a minimal intensity at day 21 after surgery. Conclusion The SDF-1/CX- CR4 biological axis plays a role in oval cell accumulation in the differentiation of hepatic oval cells, SDF-1 and its receptor CXCR4 might be important markers of hepatic stem cells.

关 键 词：肝干细胞 卵圆细胞 基质细胞衍生因子 CXCR4 

分 类 号：R575[医药卫生—消化系统]