摘要
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。
AIM：To investigate the effect of qidan tongmai tablet（QDTMT） on cardiac function and myocardial fibrosis in rats after myocardial infarction（MI）.METHODS： Sprague Dawley（SD） rats were subjected to MI by ligating the left anterior descending coronary and randomly divided into sham group,MI group,low-dose QDTMT group（MI-QDTMTL,1.0 g/kg） and high-dose QDTMT group（MI-QDTMTH,2.0 g/kg）.After 24 h of ligation,15 ml/kg saline for sham and MI groups and 1.0 g/kg or 2.0 g/kg QDTMT for MI-QDTMTL or MI-QDTMTH groups were administered twice daily.Cardiac contractile function of left ventricular end-diastolic pressure（LVEDP） and ejection factor（EF） were measured in vivo.Rats were sacrificed after 4 weeks.Collagen content in the noninfarcted area was detected by Masson＇ s trichrome stain.Transforming growth factor beta-1（TGF-β1）,collagen type 1 and collagen type 3 mRNA expressions were examined by RT-PCR in the noninfarcted area.The hydroxyproline content of the noninfarcted tissue was measured by hydroxyproline（HYP） ELISA kit for rats.RESULTS： After 4 weeks,rat cardiac function of LVEDD and EF and the heart weight/body weight（HW/BW） index in QDTMTH group and QDTMTL group were significantly better than those in MI group（P0.01;P0.05）,but poorer than those in the sham group（P0.01）.Myocardial collagen content in noninfarcted area was significantly inhibited in MI-QDTMTL group and MI-QDTMTH group（P0.01）.mRNA expression levels of TGF-β1,Col1 and Col3 in noninfarcted area were significantly inhibited in MI-QDTMTL group and MI-QDTMTH group（P0.01）.Hydroxyproline content of the noninfarcted tissue was significantly inhibited in MI-QDTMTL group and MI-QDTMTH group（P0.05）.CONCLUSION： In post-MI myocardial fibrosis,QDTMT improves cardiac function and reduces myocardial fibrosis by downregulating TGF-β1,Col1and Col3 expressions and decreasing the production of hydroxyproline.
出处
《心脏杂志》
CAS
2012年第6期681-685,共5页
Chinese Heart Journal
基金
国家自然科学基金项目资助(81072972)
关键词
芪丹通脉片
心肌梗死
心肌纤维化
重构
大鼠
qidan tongmai tablet
myocardial infarction
myocardial fibrosis
reconfiguration
rat
