N-乙酰-L-半胱氨酸对急性SiO2染尘肺组织基质金属蛋白酶表达的影响

目的观察N-乙酰-L-半胱氨酸(N-acetyl-L-cysteine,NAC)对急性SiO2染尘肺组织基质金属蛋白酶(MMPs)表达的影响。方法清洁级Wistar大鼠随机分为3组,对照组经气管注入生理盐水,损伤组和干预组注入SiO2粉尘悬液,其中干预组在注入SiO2粉尘悬液前1 h用NAC预处理。3组大鼠分别在染尘后第1,3,7,14,28天取出肺组织,应用免疫组织化学和RT-PCR方法观察其MMP-2和MMP-9蛋白及其mRNA的动态变化。结果损伤组肺组织MMP-2和MMP-9表达均较对照组增高。MMP-2蛋白表达在各时间点分别是对照组的1.440,1.811,2.379,1.672和1.412倍,差异均有统计学意义(P<0.01);mRNA表达分别是对照组的2.061,2.261,2.931,2.000和1.615倍,差异均有统计学意义(P<0.05)。MMP-9蛋白在各时间点分别是对照组的1.450,1.661,2.186,1.563和1.526倍,差异均有统计学意义(P<0.01);mRNA表达在第1,3,7,14天高于对照组,分别是对照组的1.676,2.027,2.584和2.178倍,差异均有统计学意义(P<0.01)。干预组肺组织MMP-2蛋白及mRNA表达在各时间点均低于损伤组,高于对照组,差异均有统计学意义(P<0.05或P<0.01)。MMP-9蛋白表达在各时间点低于损伤组,高于对照组;mRNA表达在第1,3,7,14天低于损伤组,高于对照组,差异均有统计学意义(P<0.05或P<0.01)。结论应用NAC可以部分抑制急性矽尘染毒肺组织表达MMP-2和MMP-9。

Effects of N-acetyl-L-cysteine on Expressions of Matrix Metalloproteinases in Lung Tissue of SiO2 Exposed Rats

Objective To study the effect of N-acetyl-L-cysteine(NAC)on the expressions of matrix metalloproteinase-2(MMP-2)and matrix metalloproteinase-9(MMP-9)in lung tissue of SiO_2 exposed rats.Methods Wistar rats were divided randomly into control group,damaged group and interventional group.Damaged group and interventional group were instilled with SiO2 suspension,while the control group with normal saline instead.The interventional group was pretreated with NAC 1 h prior to instilling SiO2.Lungs of three groups were isolated on 1,3,7,14,and 28th days after SiO2 exposure.The expression of MMP-2 and MMP-9 and dynamics of mRNA were evaluated by immunochemistry and RT-PCR.Results The expressions of protein and mRNA of MMP-2 in the damaged group were higher than those in control group on all days after SiO2 exposure(P<0.01 or P<0.05).The expression of protein of MMP-9 was higher than control groups on all days,and mRNA was higher on 1,3,7,and 14th days(P<0.01 or P<0.05).The expression of protein and mRNA of MMP-2 in interventional groups were lower than those in damaged group,and higher than the control groups on all days(P<0.01 or P<0.05).The expression of protein of MMP-9 in interventional groups were lower than damaged groups,and higher than the control groups on all days,and mRNA was lower than the damaged group,and higher than the control groups on days 1,3,7,14th(P<0.01 or P<0.05).Conclusions NAC could partly inhibit the expressions of MMP-2 and MMP-9 in SiO2 exposed rat lung.