基质金属蛋白酶及其抑制因子与扩张型心肌病的关系

Relationship of matrix metalloproteinases and tissue inhibitor of matrix metalloprpteinases to dilated cardiomyopathy disease

目的研究基质金属蛋白酶-2(MMP-2)及金属蛋白酶组织抑制因子(TIMP-1)在扩张型心肌病(DCM)中的变化,探讨血管紧张素转换酶抑制剂(ACEI)对心肌纤维化的影响及其调控机制。方法雄性SD大鼠腹腔注射阿霉素(2 mg/kg,每周1次,连续8周)建立扩张型心肌病模型。将达到DCM诊断标准的大鼠分3组:①H组(卡托普利高剂量干预组,50mg/Kg.d);②L组(卡托普利低剂量干预组,25mg/Kg.d);③C组(DCM对照组)。HE染色和苦味酸天狼星红染色观察各组大鼠心肌细胞和间质胶原变化,RT-PCR法检测心肌MMP-2及TIMP-1的表达。结果与正常对照组比较,DCM组心肌细胞坏死明显、胶原纤维和胶原容积分数增加(P<0.05);而H组和L组的胶原纤维较C组减少(P<0.05)。DCM组心肌MMP-2 mRNA表达较正常对照组显著增加(P<0.01),H组和L组较C组降低(P<0.05)。DCM组TIMP-1mRNA的表达较正常对照组降低(P<0.05),H组较C组有所增加(P<0.05)。结论 MMP-2及TIMP-1与心肌细胞外基质的重塑密切相关,ACEI有降解MMP-2的作用,可以减轻心肌间质的纤维化程度。

Objective To research the effect and significance of MMP-2 and TIMP-1 in the rat model of DCM,and to investigate the expression of MMP-2,TIMP-1 and collagen fiber during the course of DCM treated with and without ACEI.Methods 60 SD rats were divided randomly into two groups： the normal control group,and the DCM group treated with adriamycin intraperitoneally 2.0 mg/kg·week for 8 weeks.Rats with DCM were divided randomly into 3 sub groups：（1） H group：was given captopril by gavage at a dose of 50mg/kg·d for 3 weeks;（2）L group： was given captopril by gavage at a dose of 25 mg/kg·d for 3 weeks;（3）C group（DCM control group）.HE staining was used to observe the change of histopathological characteristics.The semiquantitative analysis was used to evaluate CVF.The expressions of MMP-2 and TIMP-1 were analysed with RT-PCR.Results Van Gien staining showed that CVF was increased significantly in the C group（P0.05）,but decreased significantly（in Hand L group compared with that in the C group）（P0.05）.RT-PCR showed that the expression of MMP-2 mRNA in the C group was stronger than in the normal group（P0.01）,but weaker in the H group and L group than in the C group（P 0.05）.The expression of TIMP-1mRNA in the C group was weaker than in the normal group（P0.05）.but stronger in the H group than in the C group（P0.05）.Conclusion MMP-2 and TIMP-1 are involved in the remodeling of the extra-cellular matrix in dilated cardiomyopathy.Captopril may reduce the expression of MMP-2 and upregulate the level of TIMP-1,thus playing an important role in the treatment of dilated cardiomyopathy.