丝氨酸蛋白酶抑制剂SPI-I的抗芥子气皮肤炎性损伤作用  

Inhibition of serine protease inhibitor SPI-I on sulfur mustard-induced cutaneous inflammation

作　　者：刘红岩[1] 时辉宁[1] 应莺[1] 刘艳芹[1] 郭京艳[2] 王伊文[3] 丁日高[1] 钟玉绪[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850 [2]山东省医学科学院附属医院,济南250031 [3]解放军三○二医院,北京100039

出　　处：《国际药学研究杂志》2011年第6期452-456,共5页Journal of International Pharmaceutical Research

摘　　要：目的探讨丝氨酸蛋白酶抑制剂SPI-I对芥子气皮肤炎性损伤的治疗作用。方法通过胰酶活性抑制分析及明胶酶谱法评价SPI-I的蛋白酶活性抑制作用;检测SPI-I作用后体外培养HaCaT细胞及兔在体皮肤芥子气染毒后炎性因子白细胞介素(IL)6、IL-8的水平,评价SPI-I对芥子气皮肤炎性损伤的治疗作用。结果SPI-I体外具有剂量依赖性抑制胰蛋白酶、基质金属蛋白酶(MMP)2和MMP-9的作用,SPI-I 1mg/ml能够使HaCaT细胞内IL-6、IL-8水平由给药前的46 pg/ml和0.95 ng/ml分别降低至30 pg/ml和0.25 ng/ml,芥子气染毒皮肤后连续给予SPI-I 50μg/cm23 d,皮肤IL-8水平由4.5 ng/ml降低至2.3 ng/ml。结论SPI-I具有蛋白酶抑制活性,SPI-I可通过发挥其蛋白酶抑制作用缓解芥子气诱导的炎症反应。Objective To investigate the therapeutical effect of SPI-I on cutaneous inflammation induced by sulfur mustard. Methods Chromogenic and gelatin zymography methods were used to evaluate the ability of SPI-I to inhibit activities of matrix metallo-protease（MMP） and trypsin in vitro. The production of inflammatory cytokines IL-8 and IL-6 in cultured HaCaT ceils and rabbit skin exposed to sulfur mustard were assayed by means of radiological immune analysis. Results SPI-I could dose-dependently inhibit activities of MMP-2,MMP-9 and trypsin. IL-6 and IL-8 were significantly down regulated from 46 pg/ml and 0.95 ng/ml to 30 pg/ml and 0.25 ng/ml, respectively, in mustard exposed HaCaT cells when SPI-I administered Img/ml. SPI- I treatment at dose of 50 μg/cm for consecutive 3 days following mustard exposure in rabbits suppressed a markedly increase in IL- 8 content from 4.5 ng/ml to 2.3 ng/ml. Conclusion It suggested that SPI-I partly alleviate the inflammation response to sulfur mustard owing to its serine protease inhibitory aetivity in vivo.

关 键 词：丝氨酸蛋白酶抑制剂 芥子气 皮肤 

分 类 号：R827.1[医药卫生—临床医学]