N-乙酰-L-半胱氨酸对二氧化硅致大鼠肺成纤维细胞基质金属蛋白酶表达升高的抑制

目的 探讨N-乙酰-L-半胱氨酸（NAC）对染矽尘大鼠肺成纤维细胞（LFb）基质金属蛋白酶（MMPs）MMP-2、MMP-9动态表达的影响.方法 将75只Wistar大鼠随机分为对照组、模型组和干预组.每组25只,模型组和干预组经气管注入SiO2粉尘悬液复制矽尘中毒模型,干预组在注入SiO2粉尘悬液前用NAC预处理;对照组给予同体积生理盐水.注射后1、3、7、14和28d分别获取LFb,用免疫细胞化学方法和逆转录聚合酶链式反应（RT-PCR）方法观察MMP-2、MMP-9蛋白及mRNA的动态变化.结果 （1）模型组LFb各时间点MMP-2蛋白表达高于对照组,分别是对照组的1.343、2.198、3.492、2.834和1.405倍,mRNA表达分别是对照组的2.015、4.889、7.364、3.406和2.277倍,差异均有统计学意义（P＜0.01）;在1、3、7 d MMP-9蛋白表达分别是对照组的1.372、1.286和1.306倍,在1、3 dmRNA分别是对照组的1.797和1.698倍,差异均有统计学意义（P＜0.01）.（2）干预组在各时间点MMP-2蛋白表达低于模型组,在3、7、14、28 d高于对照组（分别是对照组的1.628、2.485、2.072和1.190倍）,差异均有统计学意义（P＜0.05或P＜0.01）;在各时间点mRNA表达低于模型组,高于对照组（分别是对照组的1.612、3.062、3.930、1.976和1.419倍）,差异均有统计学意义（P＜0.05或P＜0.01）.在1、3、7 d MMP-9蛋白表达低于模型组,在3、7d高于对照组,在1、3 d mRMA表达低于模型组,高于对照组,分别是对照组的1.304和1.331倍,差异均有统计学意义（P＜0.05）.结论 NAC能抑制SiO2所致大鼠LFb的MMP-2、MMP-9蛋白及mRNA表达的升高.

Inhibition of N-acetyl-L-cysteine on expressions of matrix metalloproteinases increased by exposure to silicon dioxide in lung fibroblasts in rats

OBJECTIVE: To explore the effect of N-acetyl L-cysteine (NAC) on expressions of matrix metalloproteinases-2, 9 (MMP-2, MMP-9) in lung fibroblasts of SiO(2) exposed rats. METHODS: Seventy-five Wistar rats were divided randomly into three groups. The control group was administered with normal Saline. The model group and the interventional group were administered with SiO(2), and the interventional group was administered with NAC before SiO(2) was administered. Lung fibroblasts were isolated on day 1, 3, 7, 14, 28 after exposure to SiO(2). The expressions of MMP-2 and MMP-9 were evaluated by Immunocytochemistry and RT-PCR. RESULTS: (1) The expressions of protein and mRNA of MMP-2 in the model group were higher than that in the control group on all days after exposure to SiO(2) (P < 0.01). The expression of protein of MMP-9 was higher than the control group on day 1, 3, 7, and mRNA was higher on day 1, 3 (P < 0.01). (2) The expression of protein of MMP-2 in the interventional group was lower than the model group on all days, higher than the control group on day 3, 7, 14, 28, and the expression of mRNA was higher than the control group, lower than the model group, on all days (P < 0.05 or P < 0.01). The expression of protein of MMP-9 in the interventional group was lower than the model group on day 1, 3, 7, but higher than the control group on day 3, 7, and mRNA was lower than the model group on days 1, 3, higher than the control group (P < 0.05). CONCLUSION: NAC inhibits the expressions of MMP-2, MMP-9 in lung fibroblasts.