目的观察注射用益气复脉方(冻干)(YQFM)对慢性心力衰竭(CHF)大鼠心肌基质金属蛋白酶(MMPs)及其组织抑制因子(TlMPs)蛋白表达的影响,探讨益气复脉方对基质金属蛋白酶系统的调节作用与心肌细胞外基质(EMC)重构的相关性。方法1OO只雄性wistar大鼠中随机选取90只通过腹主动脉缩窄法制作大鼠慢性心力衰竭模型,1O只作为假手术组常规饲养。术后8W,以多普勒超声心动图检测左室射血分数(LVEF)≤60%为成模标志。成模大鼠随机分为6组:空白模型组、卡托普利组(卡托普利片4.88mg/kg)、生脉组(生脉注射液4mL/kg)及益气复脉中、低、高(520mg/kg,260mg/kg,1040mg/kg)剂量组。连续给药14d后,以HE染色法观察大鼠心肌组织病理变化以蛋白质印记法检测大鼠心肌组织中MMP-2,MMP-3,MMP-9以及TlMP-1,TlMP-2的含量。结果与假手术组比较,空白模型组心肌间质胶原纤维大量增生,EMC结构显著改变,可见局灶性纤维瘢痕;MMP-2、MMP-3、MMP-9含量显著升高(尸〈O.01),TlMP-1/2含量显著降低(P〈O.01),MMP-2/TlMP-2比值升高为假手术组的4倍~6倍。与空白模型组比较,各治疗组心肌肌柬间及血管周围胶原纤维出现轻、中度增生,MMP-2、MMP-3、MMP-9降低,TlMP-1/2升高,MMP-2/TlMP-2比值降低为假手术组的1~3倍。其中,YQFM各剂量组MMP-2、MMP-3、MMP-9含量显著低于生脉组(P〈0.05),除YQFM低剂量组MMP-2显著高于卡托普利组(P〈0.05)外,其余各YQFM组MMP-2、MMP-3、MMP-9含量与卡托普利组比较差异无统计学意义(P〉0.05)。YQFM各剂量组TlMP-2含量显著高于生脉组(P〈0.05),与卡托普利组比较差异无统计学意义(P〉0.05);YQFM各剂量组TlMP-1含量与MMP-2/TlMP-2比值显著低于卡托普利组(P〈0.05),与生脉组比较差异无统计学意义(P〉0.05);结论
Objective To investigate the regulative effect of Yiqi Fumai injection(YFI)on the activity of matrix metal oproteinase (MMPs)and tissue inhibitor of metal oproteinase(TIMPs)in rats with chronic heart failure(CHF),and explore the regulation of YFI on MMPs and its correlation with the reconstruction of myocardial extracel ular matrix(EMC).Methods One hundred Wistar rats were randomly divided into sham group (n=10)and model group(n=90).The CHF rat model was established by abdominal aortic ban-ding.After 8 weeks of operation,rats were divided into 6 groups:blank model group,captopril group,Shengmai injection(SMI) group,YFI groups(high ,medium ,low dosage).After 14 days,the myocardial pathological changes were observed by hematoxy-lin eosin (HE)staining.The contents of MMP 2,MMP 3,MMP 9,TIMP 1 and TIMP 2 in myocardial tissue were detected by western blotting.Results Compared with sham group,myocardial interstitial col agen fibers proliferated,EMC structure changed,fo-cal fibrous scars were visible in blank model group.The contents of MMP 2,MMP 3,MMP 9 and MMP 2/TIMP 2 ratio increased while the contents of TIMP 1 and TIMP 2 decreased in blank model group.Compared with blank model group group,the light and moderate proliferation of col agen fibers appeared around myocardial muscle bundle and vessels in captopril group,SMI group,YFI groups.The contents of MMP 2,MMP 3,MMP 9 and MMP 2/TIMP 2 ratio decreased while the contents of TIMP 1 and TIMP 2 increased in captopril group,SMI group,YFI groups.The contents of MMP 2,MMP 3,MMP 9 in YFI groups were lower than that in SMI group(P<0.05).The content of MMP 2 in YFI low dosage group was higher than that in captopril group(P<0.05). The contents of TIMP 2 in YFI groups were higher than that in SMI group(P<0.05).The content of TIMP 1 and MMP 2/TIMP 2 ratio in YFI groups were lower than that in captopril group(P<0.05).Conclusion The myocardial interstitial col agen proliferation and col agen structure changes induce the reconstruction of EMC in rats with CHF,which is relevant to th