不同中药复方对慢性心衰大鼠MMP-2、TIMP-2的影响

Influences of different compound formulas of Chinese medicine on MMP-2 and TIMP-2 in rats with chronic heart failure

目的研究基质金属蛋白酶2(MMP-2)及内源性基质金属蛋白酶组织抑制剂2(TIMP-2)在慢性心衰中的作用,从分子生物学角度探讨中药不同配伍对慢性心衰心室重构的影响,并进一步阐明其作用机理。方法以冠脉结扎法配合力竭式游泳、减食等方法造成大鼠慢性心衰动物模型,分成模型组、西药组、益气中药组、活血中药组、益气活血中药组、益气活血利水中药组和正常组。利用实时荧光定量PCR技术及SABC免疫组化法检测慢性心衰大鼠MMP-2、TIMP-2表达的变化情况。结果慢性心衰动物模型组大鼠心肌MMP-2表达明显升高,TIMP-2表达降低,与假手术组比较,差异有统计学意义(P<0.01);经过治疗,各用药组大鼠心肌组织MMP-2表达明显降低,TIMP-2表达升高,其中益气活血组、益气活血利水组与西药组比较,差异无统计学意义(P>0.05),且益气活血利水组疗效明显优于益气活血组(P<0.01)。结论益气活血利水中药作用于心肌组织,通过影响MMP-2、TIMP-2的表达,抑制或逆转心室重构的过程,从而达到治疗慢性心衰的目的。

Objective To study the effects of matrix metalloproteinase-2 （MMP-2） and tissue inhibitor of metalloproteinase-2 （TIMP-2） in chronic heart failure （CHF）, and investigate the influences and mechanism of different compound formulas of Chinese medicine in the ventricular remodeling of CHF at molecular biological level. Methods The rat model of CHF was established by using coronary ligation, forced swimming and underfeed. The rats were divided into mode group, Western medicinal group, supplementing qi group （Yiqi group）, activating blood group （Huoxue group）, supplementing qi and activating blood group （Yiqihuoxue group）, supplementing qi, activating blood and inducing diuresis group （Yiqihuoxuelishui group） and normal group. The changes of expressions of MMP-2 and TIMP-2 were detected by applying real-time fluorescence quantitative polymerase chain reaction （RT-PCR） and SABC immunohistochemistry technique. Results The expression of MMP-2 increased significantly and expression of TIMP-2 decreased in model group compared with normal group （P 〈 0. 01 ）. After treatment, the expression of MMP-2 decreased significantly and expression of TIMP-2 increased in all medication groups. The difference was insignificant between Yiqihuoxue group or Yiqihuoxuelishui group compared with Western medicinal group （P 〉 0. 05 ）, and curative effect was much better in Yiqihuoxuelishui group than that in Yiqihuoxue group （P 〈 0. 01 ）. Conclusion The Chinese medicinal with the actions of supplementing qi, activating blood and inducing diuresis have effect on myocardial tissue, and can inhibit or reverse ventricular remodeling to treat CHF through influencing the expressions of MMP-2 and TIMP-2.