芪丹通脉片对心肌梗死后大鼠心肌纤维化重构的影响

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目的:观察益气活血复方芪丹通脉片(qidan tongmai tablet,QDTMT)对大鼠心肌梗死(MI)后心功能及左心室非梗死区心肌纤维化的影响。方法:以结扎SD大鼠左冠脉前降支法建立MI模型,随机分为假手术(Sham)组、MI组、MI+QDTMT小剂量(MI-QDTMTL)组和MI+QDTMT大剂量(MI-QDTMTH)组。术后24 h各组均用生理盐水配制成等体积药液灌胃4周,4周后以多普勒超声评价心脏功能;测定心室的质量/体质量(HW/BW);以MAS-SON染色检测非梗死区胶原的含量;用RT-PCR法检测非梗死区转化生长因子-β1(TGF-β1)、Ⅰ型胶原蛋白(Colla-gen type 1,Col1)及Ⅲ型胶原蛋白(Collagen type 3,Col3)mRNA的表达水平。采用大鼠羟脯氨酸(HYP)的ELASA试剂盒检测非梗死区中HYP的含量。结果:①术后4周心功能:与MI组比较,MI-QDTMTL组和MI-QDTMTH组左室舒张末期内径(LVEDD)和HW/BW均降低,而射血分数(EF)升高(P<0.01或P<0.05);②非梗死区心肌胶原蛋白的含量:MI-QDTMTL组胶原和MI-QDTMTH组胶原含量均低于MI组(P<0.01);MI-QDTMTH组胶原的含量明显低于MI-QDTMTL组(P<0.01);③非梗死区TGF-β1、Col1、Col3mRNA的表达:与MI组比较,MI-QDTMTL组、MI-QDTMTH组的TGF-β1 Col1、Col3 mRNA均显著降低(P<0.01或P<0.05);MI-QDTMTH组TGF-β1、Col1、Col3mRNA的表达显著低于MI-QDTMTL组(P<0.05);④非梗死区HYP的含量:MI-QDTMTL组与MI-QDTMTH组HYP的含量低于MI组(P<0.05,P<0.01);MI-QDTMTH组HYP的含量低于MI-QDTMTL组(P<0.05)。结论:QDTMT通过下调MI交界区TGF-β1、Col1、Col3 mRNA的表达及HYP产生,进而抑制MI后非梗死区反应性胶原的过度沉积,且高剂量组比低剂量组的疗效更好,为防治MI后非梗死区心肌纤维化重构,改善心脏功能提供了新的治疗思路。 Objective: To observe the effect of qidan tongmai tablet (qidan tongmai tablet) on cardiac function and myocardial fibrosis in non-infarcted area of ​​left ventricle after myocardial infarction (MI) in rats. Methods: MI model was established by ligation of left anterior descending coronary artery in SD rats. The rats were randomly divided into Sham group, MI group, MI + QDTMT low dose group and MI + QDTMT high dose group. -QDTMTH) group. At 24 hours after operation, all rats in each group were treated with equal volume of saline solution for 4 weeks. The heart function was evaluated by Doppler ultrasound after 4 weeks. The ventricular mass and body mass (HW / BW) The expression of TGF-β1, Colla-gen type 1 (Col1) and collagen type Ⅲ (Collagen type 3, Col3) mRNA expression levels. ELASA kit using rat hydroxyproline (HYP) was used to detect the content of HYP in non-infarcted area. Results: ①After 4 weeks of cardiac function, left ventricular end-diastolic diameter (LVEDD) and HW / BW both decreased and EF increased in MI-QDTMTL group and MI-QDTMTH group compared with MI group <0.01 or P <0.05). (2) The contents of collagen in MI-QDTMTL group and MI-QDTMTH group were lower than those in MI group (P <0.01). The content of collagen in MI-QDTMTH group was significantly lower (P <0.01); ③The expression of TGF-β1, Col1 and Col3 mRNA in non-infarcted area: Compared with MI group, the mRNA expressions of Col1 and Col3 in MI-QDTMTL group and MI-QDTMTH group were significantly decreased (P <0.01 or P <0.05). The mRNA expression of TGF-β1, Col1 and Col3 in MI-QDTMTH group was significantly lower than that in MI-QDTMTL group The content of HYP in QDTMTH group was lower than that in MI group (P <0.05, P <0.01). The content of HYP in MI-QDTMTH group was lower than that in MI-QDTMTL group (P <0.05). CONCLUSION: QDTMT can inhibit the excessive deposition of reactive collagen in non-infarcted area of ​​MI by down-regulating the expression of TGF-β1, Col1 and Col3 mRNA and HYP in MI junction area, and the effect of QDTMT is better than that of low dose group After MI prevention and treatment of non-myocardial infarction myocardial fibrosis remodeling, improve cardiac function provides a new treatment ideas.
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