乙酰半胱氨酸抑制巨噬细胞诱导的泡沫细胞基质金属蛋白酶MMP2和MMP9的表达

目的：探讨乙酰半胱氨酸(NAC)对巨噬细胞诱导的泡沫细胞基质金属蛋白酶MMP2和MMP9的抑制作用。方法：10只大白兔用球囊损伤主动脉进行球囊损伤，用高胆固醇食物（0.5%高胆固酶，4.5%椰子油）饲养8周，然后从主动脉粥样斑块中分离出巨噬细胞诱导的泡沫细胞,在无牛血清DMEM细胞培养液中加入 10 mmol?L^-1NAC为实验组，对照组(未经球损伤的组织细胞)不加NAC。两组均在37℃、5% CO₂的细胞培养箱中培养24 h、48 h和4 d后收集培养液，应用酶谱和免疫组化方法分别检测培养液和斑块主动脉粥样局部组织中的MMP2和MMP9的表达。结果：实验组24 h、48 h和4 d Pro-MMP9［分别为(654±33.5)、(780±65.0)和(799±48.9)INT?mm^-2］低于对照组 ［分别为(1 455±50.9)、(15 615±52.0)^-2和(1 467±48.8)INT?mm^-2］(P<0.01)；实验组24 h、48 h和4 d　MMP2分别为［(221±25.3)、(224±25.0)和(202±33.9)INT?mm^-2］低于对照组［分别为(467±34.3)、(561±42.0)和(671±34.8)INT?mm^-2］(P<0.01)(P<0.01)。兔疸组化方法显示了巨噬细胞MMP２、MMP9均为阳性染色(+)。结论：NAC减少巨噬细胞诱导的泡沫细胞基质金属蛋白酶（MMPs）的表达,提示NAC可作为冠心病治疗的一个新靶点。 

Inhibitory effcts of N-aetyl-cysteine on matrix metalloproteinase expressions of macrophage-derived foam cells

Objective To study the inhibitory effects of N-aetyl-cysteine(NAC) on the expressions of matrix metalloproteinases (MMPs) of macrophage-derived foam cells (FCs). Methods The hypercholesterolemic (0.5% cholesterol and 4.5% coconut) rabbit model of atherosclerosis was used to investigate the gelatinolytic activity associated with FCs,which were isolated from rabbit atheroma. FCs were maintained in culture medium for 24 h up to 4 d, NAC (10 mmol·L~ -1 ) was added to culture medium of FCs.The expresions of MMPs were detected with SDS PAGE and immunohistochemistry assay.Results The Pro-MMP9 concentrations in NAC group at 24 h,48 h and 4 d(654±33.5),(780±65.0) and (799±48.9)INT·mm~ -2 ]were lower than those in control group(1455±50.9),(15 615±52.0) and (1 467±48.8)INT·mm~ -2 ] (P<0.01). At 24 h,48 h and 4 d the concentrations of MMP2 in NAC group (221±25.3),(224±25.0) and (202±33.9) INT·mm~ -2 ]were lower than those in control group 467±34.3),(651±42.0) and (671±34.8)INT·mm~ -2 ](P<0.01) ,the immunohistochemical result showed MMP2(+ ), macrophage(+), and MMP9(+).Conclusion This newly described action of antioxidant therapy might be useful to inhibit matrix degradation and to improve vascular stability. NAC represents an attractive therapeutic target.