摘要
目的:砒石是化腐生肌的常用中药,其主要成分是三氧化二砷(As2O3)。本研究通过观察As2O3对基质金属蛋白酶(MMPs)活性、基质金属蛋白酶组织抑制因子-1(TIMP-1)及转化生长因子β1(TGF-β1)表达影响,探讨化腐中药能否调节胶原代谢,从而治疗慢性皮肤溃疡。方法:明胶酶谱法检测大鼠中性粒细胞(PMNs)来源的MMP-9活性、人成纤维细胞(hFb)分泌的MMP-1、MMP-2的活性,免疫细胞化学法检测hFb TIMP-1、TGF-β1的表达。结果:As2O3浓度在50mg/L时可以提高大鼠PMNs来源的MMP-9的活性(P<0.01);在0.8mg/L可以提高hFb分泌的MMP-1、MMP-2的活性(分别P<0.01);同时As2O3作用于hFb6h、12h、18h后,TIMP-1、TGF-β1表达持续降低(P<0.01)。结论:As2O3在一定范围内可提高PMNs来源的MMP-9的活性;也可提高hFb分泌的MMP-1、MMP-2的活性,同时抑制hFbTIMP-1、TGF-β1的表达。提示砷类制剂可通过提高多种MMPs的活性,降低TIMP-1的表达从而发挥化腐作用。
AIM： To observe the effects of arsenic trioxide （As2O3 ） on activities of matrix metalloproteinases （MMPs）, expression of tissue inhibitor of metalloproteinase - 1 （TIMP - 1 ） and transforming growth factor betal （TGF - β1 ） in human fibroblast （hFb）, and to discuss weather As2O3 promotes the healing of chronic skin ulcer through regulating collagen metabolism. METHODS ： Zymography was used for testing activity of MMP - 9 deriving from rat polymorphonuclear neutrophils （PMNs） and activities of MMP - 1, MMP - 2 secreted by hFb. Immunocytochemical method was used to determine the expressions of TIMP - 1 and TGF - β1. RESULTS： At the concentration of 50 mg/L, As2O3 elevated the activity of MMP - 9 （ P 〈 0.01 ）. At the concentration of 0. 8 mg/L, As2O3 increased the activities of MMP - 1 and MMP-2 （P〈0.01, respectively）. After hFb was cultured with As2O3 for 6 h, 12 h and 18 h, the expressions of TIMP - 1 and TGF - β1 decreased continuously （P 〈 0. 01 ）. CONCLUSION ： As2O3 elevates the activities of MMP - 1, MMP -2 and MMP- 9, also inhibits the expressions of TIMP- 1 and TGF- β1, suggesting that arsenic preparation may exert positive effect on healing chronic skin ulcer through regulating collagen metabolism.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2008年第11期2209-2213,共5页
Chinese Journal of Pathophysiology
基金
北京市自然科学基金资助项目(No.7072014)
