CAJ | 학술논문

目的研究血管紧张素转换酶抑制剂卡托普利和血管紧张素Ⅱ(AngⅡ)受体拮抗剂氯沙坦对AngⅡ诱导的血管平滑肌细胞基质金属蛋白酶-1(MMP-1)和MMP-9 mRNA表达的干预作用.方法体外原代培养雄性Wistar大鼠胸主动脉血管平滑肌细胞,分为对照组、AngⅡ组、卡托普利组、氯沙坦组和卡托普利与氯沙坦联合应用组.收集各组培养终点细胞,以反转录聚合酶链反应(RT-PCR)检测所收集标本中MMP-1和MMP-9 mRNA的表达,观察不同浓度AngⅡ和作用时间对血管平滑肌细胞MMP-1、MMP-9 mRNA表达的影响及卡托普利、氯沙坦的干预作用.结果 MMP-1 mRNA表达随AngⅡ浓度增加及作用时间延长而增加(P＜0.05),AngⅡ浓度为10-6mol/L时最为显著(P＜0.01).一定浓度的卡托普利(5×10-6mol/L)和氯沙坦(5×10-6mmol/L)可抑制AngⅡ的作用(P＜0.05,P＜0.01);AngⅡ为10-7、10-6、10-5、10-4mol/L时,MMP-9 mRNA表达量分别为0.47±0.03、0.86±0.04、0.94±0.14和1.12±0.19,与对照组0.10±0.04比较,差异有统计学意义(P＜0.05或P＜0.01).卡托普利和氯沙坦可抑制AngⅡ对血管平滑肌细胞分泌的MMP-9 mRNA的促进表达作用,以卡托普利和氯沙坦联合应用时抑制作用最强;MMP-9 mRNA的表达随AngⅡ作用时间延长而增加;MMP-9 mRNA较MMP-1表达早.结论 AngⅡ可以诱导血管平滑肌细胞分泌的MMP-1和MMP-9 mRNA高表达,且存在剂量和时间依赖性.卡托普利、氯沙坦可抑制AngⅡ诱导的血管平滑肌细胞MMP-1和MMP-9 mRNA高表达;卡托普利和氯沙坦联合应用时抑制作用最强;这种抑制作用与作用时间相关.
목적 연구혈관긴장소전환매억제제잡탁보리화혈관긴장소Ⅱ(AngⅡ)수체길항제록사탄대AngⅡ유도적혈관평활기세포기질금속단백매-1(MMP-1)화MMP-9 mRNA표체적간예작용.방법 체외원대배양웅성Wistar대서흉주동맥혈관평활기세포,분위대조조、AngⅡ조、잡탁보리조、록사탄조화잡탁보리여록사탄연합응용조.수집각조배양종점세포,이반전록취합매련반응(RT-PCR)검측소수집표본중MMP-1화MMP-9 mRNA적표체,관찰불동농도AngⅡ화작용시간대혈관평활기세포MMP-1、MMP-9 mRNA표체적영향급잡탁보리、록사탄적간예작용.결과 MMP-1 mRNA표체수AngⅡ농도증가급작용시간연장이증가(P＜0.05),AngⅡ농도위10-6mol/L시최위현저(P＜0.01).일정농도적잡탁보리(5×10-6mol/L)화록사탄(5×10-6mmol/L)가억제AngⅡ적작용(P＜0.05,P＜0.01);AngⅡ위10-7、10-6、10-5、10-4mol/L시,MMP-9 mRNA표체량분별위0.47±0.03、0.86±0.04、0.94±0.14화1.12±0.19,여대조조0.10±0.04비교,차이유통계학의의(P＜0.05혹P＜0.01).잡탁보리화록사탄가억제AngⅡ대혈관평활기세포분비적MMP-9 mRNA적촉진표체작용,이잡탁보리화록사탄연합응용시억제작용최강;MMP-9 mRNA적표체수AngⅡ작용시간연장이증가;MMP-9 mRNA교MMP-1표체조.결론 AngⅡ가이유도혈관평활기세포분비적MMP-1화MMP-9 mRNA고표체,차존재제량화시간의뢰성.잡탁보리、록사탄가억제AngⅡ유도적혈관평활기세포MMP-1화MMP-9 mRNA고표체;잡탁보리화록사탄연합응용시억제작용최강;저충억제작용여작용시간상관.
Objective To investigate the effect of angiotensin converting enzyme inhibitor (ACEI) captopril and angiotensin Ⅱ receptor antagonist losartan on the mRNA expression of matrix metalloproteinase (MMP)-1 and MMP-9 in vascular smooth muscle cells induced by angiotensin Ⅱ (Ang Ⅱ ).Methods Male Wistar rats' thoracic aortic vascular smooth muscle cells were cultured in vitro.The cultured cells were divided in to control group,Ang Ⅱ group,captopril group,losartan group,and captopril plus losartan group.Cells in all groups were collected at the culture end-point.MMP-1 and MMP-9 mRNA expressions were detected by RT-PCR method in the collected specimens,and the effects of Ang Ⅱ on MMP-1 and MMP-9 mRNA expression and the intervention effects of captopril and losartan were observed in different Ang Ⅱ concentrations and different action times to vascular smooth muscle cells.Results ( 1 ) MMP-1 mRNA expression gradually increased along with the increments of Ang Ⅱ concentration and the action time (P＜0.05),and the most significant concentration was 10-6 mol/L (P＜0.01).(2)Captopril (5 × 10-6 mol/L) and losartan (5 × 10-6mol/L) inhibited the action of AngⅡ (P＜0.05,P＜0.01).MMP-9 mRNA expression was 0.47±0.03 ,0.86 ± 0.04,0.94±0.14 and 1.12±0.19 vs.0.10±0.04 (P＜0.05,P＜0.01) respectively when Ang Ⅱ concentration was 10-7 ,10-6 ,10-5 and 10-4 mol/L respectively.Captopril (5 × 10-6mol/L) and losartan (5 × 10-6 mol/I) significantly inhibited the MMP-9 mRNA expression which was stimulated by Ang Ⅱ (P＜0.05,P＜0.01),especially in captopril plus losartan group.The MMP-9 mRNA expression increased with the prolonging of stimulating time of Ang Ⅱ,MMP-9 mRNA expression was earlier than that of MMP-1.Conclusions AngⅡ increases the expression of MMP-1 and MMP-9 of vascular smooth muscle cells in a dose-and time-dependence manner.Captopril and losartan inhibit the MMP-1 and MMP-9 mRNA expression of vascular smooth muscle cells induced by Ang Ⅱ ,and the inhibition is the strongest when losartan was combined with captopril.The inhibitive effects is positively correlated to action time.