哮喘大鼠中性粒细胞基质金属蛋白酶9和血清基质金属蛋白酶抑制剂-1的表达及地塞米松对其的影响

Expression levels of matrix metalloproteinase-9 in blood polymorphonuclear leucocyte and serum TIMP-1 and the effect of dexamethasone on them in rat asthma models

目的:观察基质金属蛋白酶9(MMP-9)在哮喘大鼠血中性粒细胞(PMN)中的表达及地塞米松对其的影响,探讨血PMN中MMP-9和基质金属蛋白酶抑制剂-1(TIMP-1)的相关性。方法:采用哮喘大鼠模型,随机分成哮喘组、正常对照组、地塞米松治疗组,对血PMN进行分离纯化,免疫细胞化学法检测MMP-9的表达水平,ELISA法检测血清TIMP-1的蛋白浓度。结果:哮喘组(0.196±0.011,OD值)和地塞米松治疗组(0.135±0.008,OD值)中MMP-9的表达水平均显著高于正常对照组(0.100±0.010,OD值)(P<0.01),地塞米松治疗组MMP-9的表达水平显著低于哮喘组(P<0.01)。哮喘组[(34.96±4.54)ng/mL]血清TIMP-1的表达水平分别显著高于正常对照组[(26.14±3.43)ng/mL]和地塞米松治疗组[(29.89±3.43)ng/mL](均P<0.01),地塞米松治疗组TIMP-1的表达水平显著高于正常对照组(P<0.05)。MMP-9与TIMP-1的表达水平呈显著正相关(n=29,r=0.741,P<0.01)。结论:PMN能合成MMP-9,且哮喘时其合成水平增加。PMN可能部分通过MMP-9起作用来参与哮喘的炎症过程,其合成功能可以被地塞米松所抑制。MMP-9及其抑制物TIMP-1共同参与哮喘的发病机制。

AIM： To investigate the expression of matrix metalloproteinase-9 （MMP-9） in blood polymorphonuclear leukocyte （PMN） and the effect of dexamethasone on them in rat asthma models. To explore the relationship between MMP-9 in PMN and its inhibitor matrix metallo-preteinase inhibitor-1 （ TIMP-1 ）. METHODS： The rat models of asthma were randomly divided into asthma group （group A）, control group （group C） and dexamethasone treated group （group D）. Blood PMN was isolated and purified. The expression of MMP-9 was detected by immunocytochemical method in blood PMN. The concentration of TIMP-1 protein was detected by ELISA. RESULTS： The levels of MMP-9 in PMN in group A （OD = 0. 196 ± 0.011） and in group D（OD = 0.135 ±0.008） were significantly higher than those in group C（OD = 0. 100 ＋0.010）（P 〈0.01）. The levels of MMP-9 in PMN in group D were significantly lower than those in group A. The levels of TIMP-1 protein in group A[ （34.96 _＋4.54） ng/mL] were significantly higher than those in group C [ （ 26.14 ＋ 3.43 ） ng/mL ] and in group D [（29.89＋3.43） ng/mL] （P 〈0.01）. The levels of TIMP-1 protein in group D were significantly higher than those in group C （ P 〈 0.05）. There was signifi- cant positive correlation between blood MMP-9 in PMN protein expression level and concentration of TIMP-1 protein（n=29, r=0.741,P〈0.01）. CONCLU- SION： MMP-9 protein can be synthesized by PMN, and expression levels of MMP-9 are increased in rat asthma. PMN are involved in asthmatic inflammation and maybe by increasing synthesis of MMP-9. But this function of PMN can be inhibited by dexamethasone. MMP-9 and its inhibitor TIMP-1 may take part in the pathogenesis of asthma exacerbation.