中华心血管病杂志
中華心血管病雜誌
중화심혈관병잡지
Chinese Journal of Cardiology
2009年
10期
887-891
,共5页
邢晓倩%徐健%吕雄文%黄艳%朱鹏里
邢曉倩%徐健%呂雄文%黃豔%硃鵬裏
형효천%서건%려웅문%황염%주붕리
心力衰竭%充血性%基质金属蛋白酶%心肌%纤维化%干预性研究
心力衰竭%充血性%基質金屬蛋白酶%心肌%纖維化%榦預性研究
심력쇠갈%충혈성%기질금속단백매%심기%섬유화%간예성연구
Heart failure%congestive%Matrix metalioproteinases%Myocardium%Fibrosis%Intervention studies
目的 探讨心力衰竭(心衰)时心脏基质金属蛋白酶2(MMP-2)、9(MMP-9)及其组织抑制因子1(TIMP-1)、2(TIMP-2)基因表达及其与心肌纤维化的关系.方法 用降主动脉缩窄术建立心衰模型.SD大鼠随机分成6组.分别在氯沙坦5 mg/kg、辛伐他汀2 mg/kg以及两药合用(联合投药组)投药后1、3,5周动态测定左室舒张末期内径、左室收缩末期内径及左室后壁厚度、左室短轴缩短率.ELISA法检测B型利钠肽浓度.Masson染色观察心肌胶原情况.RT-PCR法检测心室MMP-2、MMP-9和TIMP-1、TIMP-2基因表达.结果 投药后5周各组胶原容积分数比较差异有统计学意义(P<0.01),投药各组较降主动脉缩窄(模型)组下降(P<0.05),尤其联合投药组下降更明显(P<0.01).MMP-2 mRNA和MMP-9 mBNA在投药各组与模型组差异无统计学意义(P>0.05);但TIMP-1 mRNA和TIMP-2 mRNA在投药各组明显低于模型组(P<0.01),联合投药组降低更明显(P<0.05).结论 心衰模型大鼠MMP-2 mRNA、MMP-9 mRNA和TIMP-1 mRNA、TIMP-2 mRNA表达升高可能是压力负荷大鼠心肌胶原含量增加的分子机制之一,氯沙坦、辛伐他汀以及联合投药均能下调TIMP-1 mRNA、TIMP-2 mRNA水平,缓解心肌重构,尤其联合投药组效果更明显.
目的 探討心力衰竭(心衰)時心髒基質金屬蛋白酶2(MMP-2)、9(MMP-9)及其組織抑製因子1(TIMP-1)、2(TIMP-2)基因錶達及其與心肌纖維化的關繫.方法 用降主動脈縮窄術建立心衰模型.SD大鼠隨機分成6組.分彆在氯沙坦5 mg/kg、辛伐他汀2 mg/kg以及兩藥閤用(聯閤投藥組)投藥後1、3,5週動態測定左室舒張末期內徑、左室收縮末期內徑及左室後壁厚度、左室短軸縮短率.ELISA法檢測B型利鈉肽濃度.Masson染色觀察心肌膠原情況.RT-PCR法檢測心室MMP-2、MMP-9和TIMP-1、TIMP-2基因錶達.結果 投藥後5週各組膠原容積分數比較差異有統計學意義(P<0.01),投藥各組較降主動脈縮窄(模型)組下降(P<0.05),尤其聯閤投藥組下降更明顯(P<0.01).MMP-2 mRNA和MMP-9 mBNA在投藥各組與模型組差異無統計學意義(P>0.05);但TIMP-1 mRNA和TIMP-2 mRNA在投藥各組明顯低于模型組(P<0.01),聯閤投藥組降低更明顯(P<0.05).結論 心衰模型大鼠MMP-2 mRNA、MMP-9 mRNA和TIMP-1 mRNA、TIMP-2 mRNA錶達升高可能是壓力負荷大鼠心肌膠原含量增加的分子機製之一,氯沙坦、辛伐他汀以及聯閤投藥均能下調TIMP-1 mRNA、TIMP-2 mRNA水平,緩解心肌重構,尤其聯閤投藥組效果更明顯.
목적 탐토심력쇠갈(심쇠)시심장기질금속단백매2(MMP-2)、9(MMP-9)급기조직억제인자1(TIMP-1)、2(TIMP-2)기인표체급기여심기섬유화적관계.방법 용강주동맥축착술건립심쇠모형.SD대서수궤분성6조.분별재록사탄5 mg/kg、신벌타정2 mg/kg이급량약합용(연합투약조)투약후1、3,5주동태측정좌실서장말기내경、좌실수축말기내경급좌실후벽후도、좌실단축축단솔.ELISA법검측B형리납태농도.Masson염색관찰심기효원정황.RT-PCR법검측심실MMP-2、MMP-9화TIMP-1、TIMP-2기인표체.결과 투약후5주각조효원용적분수비교차이유통계학의의(P<0.01),투약각조교강주동맥축착(모형)조하강(P<0.05),우기연합투약조하강경명현(P<0.01).MMP-2 mRNA화MMP-9 mBNA재투약각조여모형조차이무통계학의의(P>0.05);단TIMP-1 mRNA화TIMP-2 mRNA재투약각조명현저우모형조(P<0.01),연합투약조강저경명현(P<0.05).결론 심쇠모형대서MMP-2 mRNA、MMP-9 mRNA화TIMP-1 mRNA、TIMP-2 mRNA표체승고가능시압력부하대서심기효원함량증가적분자궤제지일,록사탄、신벌타정이급연합투약균능하조TIMP-1 mRNA、TIMP-2 mRNA수평,완해심기중구,우기연합투약조효과경명현.
Objective To investigate the effects of simvastatin(Sim) and losartan(Los) on cardiac fibrosis and myocardial expression of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in pressure overloaded rat hearts. Methods The pressure overload model was induced by descending aortic constriction (DAC) in rats. SD rats were randomized into 6 groups (n=20 each) : normol control group, control sham group, DAC group, Los group (DAC+Los, 5 mg/kg), Sire group ( DAC + Sire, 2 mg/kg), Los + Sire group (DAC+Los+Sire, Los 5 mg/kg, Sire 2 mg/kg). Water, Los or Sire drug was administrated by garage daily beginning from day 5 after operation for 30 days. Collagen was measured on Masson stained myocardial sections, and the level of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in left ventricle were detected by RT-PCR. Results Collagen volume fraction (CVF) in DAC group was significantly higher than the normal control and sham groups (P<0.01) which could be significantly reduced by Los and Sire (P<0.05), especially in DAC + Los + Sire group (P<0.01). The levels of myocardial MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA were also significantly higher in DAC group than in normal control and sham groups (P<0.01). Treatment Sim and Los alone and especially in combination significantly decreased the TIMP-1 mRNA, TIMP-2 mRNA expressions (P<0.01) while MMP-2 mRNA, MMP-9 mRNA levels remained unchanged (P>0.05). Conclusion Upregulation of myocardial MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA expressions might contribute to myocardial fibrosis in this model, Sire and Los significantly inhibited myocardial fibrosis possibly by downregulating myocardial TIMP-1 mRNA, TIMP-2 mRNA expressions in this model.
