甘草酸对胰腺星状细胞细胞外基质代谢调节作用的研究  

Effect of glycyrrhizin on extracellular matrix metabolism in pancreatic stellate cells

作　　者：吴恺[1] 徐刚[1] 王兴鹏[1] 

机构地区：[1]上海交通大学医学院附属第一人民医院消化疾病研究室,200080

出　　处：《中华消化杂志》2007年第11期728-731,共4页Chinese Journal of Digestion

基　　金：上海市卫生局课题资助项目(024016)

摘　　要：目的观察甘草酸对胰腺星状细胞(PSC)合成分泌Ⅰ型胶原、基质金属蛋白酶(MMP)及其抑制物(TIMP)的影响,探讨其抗胰腺纤维化的作用机制。方法采用组织块培养法分离培养活化的PSC,培养基中添加0、1、2.5、5和10mg/ml不同剂量的甘草酸,培养24h后分别留取上清和细胞。采用放射免疫法测定上清中Ⅰ型胶原含量;明胶酶谱和反式明胶酶谱测定浓缩上清中MMP-2、MMP-9和TIMP-1、TIMP-2的表达;RT-PCR测定MMP-2、MMP-9、FIMP-1、TIMP-2和Ⅰ型胶原mRNA的表达。结果甘草酸可明显抑制PSC中Ⅰ型胶原含量,以5mg/ml时抑制最明显[从(52±10)ng/ml降至(35±8)ng/ml]。明胶酶谱和RT-PCR显示,PSC有MMP-2、MMP-9和TIMP-2基因和蛋白表达,而TIMP-1仅有基因表达。甘草酸可抑制MMP-2和MMP-9蛋白表达,而MMP-9基因表达未受明显抑制;甘草酸对TIMP-1和TIMP-2基因表达无明显作用,对TIMP-2蛋白的表达仅在10mg/ml浓度时有部分抑制。结论甘草酸可能通过抑制Ⅰ型胶原合成、减少MMP-2和MMP-9表达等途径抑制PSC中细胞外基质的代谢。Objective To study the mechanism and effect of glycyrrhizin（Gly）on synthesis of type 1 collagen matrix metalloproteinas（MMP） and tissue inhibitor of metalloproteinas （TIMP） in pancreatic stellate cells（PSCs）. Methods The activated PSCs seperated by tissue culture method were cultured with different doses of Gly（0, 1, 2.5, 5 or 10mg/ml）for 24 h. The type Ⅰ collagen was detected by radioimmunoassay. The expressions of MMP-2, MMP-9 and TIMP-1, TIMP-2 proteins were measured by gelatin zymography and reverse zymography, respectively, and gene expressions were determined by RTPCR. Results The level of type [ collagen was decreased by Gly at different concentrations, especially at 5 mg/ml[decreased from（52 ± 10）ng/ml to（35 ± 8）ng/ml]. Both gene and protein expressions of MMP-2, MMP-9 and TIMP-2 were found in PSCs, but only gene expression of TIMP-1 was found in PSCs. The protein expressions of MMP-2 and MMP-9 were inhibited by Gly, but gene expression of MMP-9, TIMP-1 and TIMP-2 were not inhibited. The TIMP-2 protein expression was partly inhibited by Gly at 10 mg/ml. Conclusion Gly may potentially regulates extracellular matrix metabolism by inhibiting synthesis of type Ⅰ collagen and expression of MMP-2 and MMP-9.

关 键 词：胰腺炎 星状细胞 甘草酸 细胞外基质 

分 类 号：R576[医药卫生—消化系统]