乙酰半胱氨酸对兔动脉粥样硬化斑块形成的干预作用

目的 探讨乙酰半胱氨酸(NAC)对兔动脉粥样硬化中基质金属蛋白酶(MMP)的干预作用.方法 新西兰雄性白兔18只给予高脂饮食喂养,体外动脉导管球囊损伤兔颈内动脉,建立兔动脉粥样硬化模型.分为3组:对照组和2种剂量(15、30 mg/kg)NAC干预组.免疫组织化学法观察动脉粥样硬化斑块形成及MMP、氧化低密度脂蛋白(ox-LDL)的分布情况,用酶联免疫吸附试验榆测血清中ox-LDL水平.用酶谱法检测血清中MMP-2及MMP-9的表达.用逆转录聚合酶链反应及琼脂糖凝胶电泳法检测组织中MMP-2及MMP-9的mRNA表达.结果 NAC(15 mg/kg)组比对照组新生内膜面积减少[(1.79±0.24)(2.78±0.17)mm2]、最大内膜厚度减少[(0.16±0.01)比(0.24.4±O.02)mm]、血管腔面积增加[(0.58±0.10)比(0.33±0.11)mm2均P<0.05].第8周时NAC(30mg/kg)组ox-LDL水平[(30.5 4±1.2)mmol/L]较对照组[(36.2±1.8)mmoL/L]下降16%(P<0.01).血清pro-MMP-2,MMP-2,pro-MMP-9水平(INT/mm2:分别为311 ±19、208 4±8、283 ±7)较对照组明显下降(分别为619±17、574±8、564 ±10,均P<0.01).NAC(30 mg/kg)组MMP-2、MMP-9mRNA表达[分别为(2.4 ±0.4)、(2.8±0.2)]比对照组下降[(3.4 ±0.3)、(3.7±0.5),均P<0.05].结论 NAC能抑制动脉粥样硬化的形成并能抑制ox-LDL、MMP-9、MMP-2血清水平及下调mRNA的表达.

Inhibitory effect of N-acetylcysteine upon atherosclerotic processes in rabbit carotid

Objective To discuss the effect of N-acetylcysteine (NAC) upon matrix metalloproteinases (MMP) in the atherosclerotic processes in rabbit carotid. Methods The atherosclerotic models were generated in vitro by injuring rabbit internal carotid with arterial canal balloon. These rabbits were divided into 3 groups (15 mg/kg NAC, 30 mg/kg NAC and control group) and treated for 8 weeks.HE staining and immunohistochemistry were used to observe the plaque formation and the distribution of MMPs and ox-LDL. ELISA was used to detect the level of ox-LDL. And the protein levels of MMP-2 and MMP-9 in rabbit venous blood were detected by SDS PAGE zymography. The mRNA level of MMP-2 and MMP-9 were measured by RT-PCR and electrophoresis. Results As compared with the control group, NAG (15 mg/kg) group had a reduction of neointima of arterial lumen [(1.79 ±0. 24) vs (2.78 ±0. 17)mm2].A decrease of endothelial thickness [(0. 16± 0.01) vs (0.24 ± 0. 02) mm2] and an increase of vascular cavity transverse [(0.58± 0.10) vs (0.33 ± 0.11) mm2] (P < 0.05) were observed. At week 8, the oxLDL levels decreased by 16% in NAC (30 mg/kg) group [(30.5± 1.2) vs (36.2 ± 1.8) mmol/L](P < 0.01). Serum levels of pro-MMP-2, MMP-2 and pro-MMP-9 decreased markedly [INT/mm2 : (311 ±19,208± 8,283±7 vs 619 ±17,574 ± 8,564 ± 10) respectively, P < 0.01] in NAC (30 mg/kg) group.The levels of mRNA expression of MMP-2 and MMP-9 were (2.4±0.4, 2.8 ±0.2)vs(3.4 ±0.3, 3.7 ±0.5) respectively (P < 0.05). Conclusion NAC inhibits the atherosclerotic formation, suppresses the levels of ox-LDL, MMP-9 and MMP-2 and downgrades the expression of matrix metalloproteinase mRNA.