CAJ | 학술논문

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.
목적 탐토을선반광안산(NAC)대토동맥죽양경화중기질금속단백매(MMP)적간예작용.방법 신서란웅성백토18지급여고지음식위양,체외동맥도관구낭손상토경내동맥,건립토동맥죽양경화모형.분위3조:대조조화2충제량(15、30 mg/kg)NAC간예조.면역조직화학법관찰동맥죽양경화반괴형성급MMP、양화저밀도지단백(ox-LDL)적분포정황,용매련면역흡부시험유측혈청중ox-LDL수평.용매보법검측혈청중MMP-2급MMP-9적표체.용역전록취합매련반응급경지당응효전영법검측조직중MMP-2급MMP-9적mRNA표체.결과 NAC(15 mg/kg)조비대조조신생내막면적감소[(1.79±0.24)(2.78±0.17)mm2]、최대내막후도감소[(0.16±0.01)비(0.24.4±O.02)mm]、혈관강면적증가[(0.58±0.10)비(0.33±0.11)mm2균P<0.05].제8주시NAC(30mg/kg)조ox-LDL수평[(30.5 4±1.2)mmol/L]교대조조[(36.2±1.8)mmoL/L]하강16%(P<0.01).혈청pro-MMP-2,MMP-2,pro-MMP-9수평(INT/mm2:분별위311 ±19、208 4±8、283 ±7)교대조조명현하강(분별위619±17、574±8、564 ±10,균P<0.01).NAC(30 mg/kg)조MMP-2、MMP-9mRNA표체[분별위(2.4 ±0.4)、(2.8±0.2)]비대조조하강[(3.4 ±0.3)、(3.7±0.5),균P<0.05].결론 NAC능억제동맥죽양경화적형성병능억제ox-LDL、MMP-9、MMP-2혈청수평급하조mRNA적표체.
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.