生长抑素及奥曲肽对肝星状细胞基质代谢的负调节作用  

Negative regulatory effects of somatostatin and its analogue on the extracellular matrixes metabolism in hepatic stellate cells

作　　者：潘勤[1] 李定国[1] 陆汉明[1] 徐芹芳[1] 

机构地区：[1]上海交通大学附属新华医院消化内科,上海200092

出　　处：《中国病理生理杂志》2008年第6期1183-1187,共5页Chinese Journal of Pathophysiology

基　　金：上海市科委基金资助项目(No004119047)

摘　　要：目的:探讨生长抑素(SST)及其类似物奥曲肽(OCT)对大鼠肝星状细胞(HSCs)细胞外基质(ECM)代谢的影响。方法:采用原位杂交、[3H]-脯氨酸掺入、酶联免疫吸附(ELISA)、免疫细胞化学染色法,分别检测SST、OCT处理后HSC中I型及III型胶原mRNA、基质金属蛋白酶(MMP)、基质金属蛋白酶抑制物(TIMP)的水平和胶原合成率,以及培养上清液中层黏连蛋白(LM)、透明质酸(HA)、III型前胶原(PCIII)的含量。结果:10-7mol/L-10-6mol/LSST、10-7mol/L-10-5mol/LOCT均可显著抑制HSC中I、III型胶原mRNA及胶原的表达,明显减少HA、LM、PCIII的分泌,且呈现剂量依赖关系。10-6mol/LSST及10-6mol/L-10-5mol/LOCT共孵育还可使HSC的TIMP-1合成明显下降,从而降低MMP-1/TIMP-1比例。结论:SST及其类似物可通过转录、翻译水平的调节,减少ECM合成,加速其降解,从而发挥抗肝纤维化作用。AIM： To evaluate the negative regulatory effects of somatostatin （SST） and octreotide （OCT） on the extracellular matrixes （ECM） metabolism in rat hepatic stellate cells （HSCs）. METHODS： HSCs were treated with different concentrations of SST or OCT. The mRNA levels of collage type I, III and the intraeellular expression of collagen, matrix metalloproteinase - 1 （ MMP - 1 ）, tissue inhibitor of metalloproteinase - 1 （ TIMP - 1 ） in activated HSCs were as- sessed by in situ hybridization （ ISH）, [^3 H ] - proline incorporation and immunocytochemistry, respectively. In addition, levels of hyaluronic acid （ HA）, laminin （LM）, and procollagen type III （PCIII） in the culture supernatant of HSCs were also detected by enzyme-linked immunosorbont assay. RESULTS： Both SST （10^-7 mol/L- 10^-6 mol/L） and OCT （10^-7 mol/L- 10^-5 mol/L） markedly down -regulated the transcription of collagen type I, III, and the production of col- lagen, HA, LM, PCIII in HSCs in a dose-dependent manner. Furthermore, HSCs treated with SST （10^-6 mol/L） and OCT （ 10^ -6 mol/L - 10^-5 mol/L） significantly reduced TIMP - 1 level, which resulted in an elevated ratio of MMP - 1/ TIMP - 1. CONCLUSION： SST and its analogy inhibit the synthesis of ECM and enhance its degradation both at transcriptional and translational levels.

关 键 词：生长抑素 奥曲肽 肝星状细胞 细胞外基质 

分 类 号：R363[医药卫生—病理学]