基质金属蛋白酶诱导因子在阿霉素心肌病大鼠左室心肌中的表达与意义

目的研究基质金属蛋白酶诱导因子在阿霉素心肌病大鼠左室心肌中的表达与意义。方法35只雄性Wist-ar大鼠分两组：正常对照组（CON组,n=10）和阿霉素心肌病组（ADR-DCM组,n=25）。ADR-DCM模型建立方法：阿霉素2.5 mg/kg,尾静脉注射,每周1次,连续10周。CON组注射相同体积的生理盐水注射液。12周时进行超声检测评价其心功能,HE染色观察其组织学变化,Western印迹分析检测基质金属蛋白酶诱导因子（EMMPRIN）蛋白表达,明胶酶谱法检测MMPs活性。结果ADR-DCM组大鼠死亡率为40%（10/25）,CON组无死亡。ADR-DCM组大鼠左室舒张末期内径（LVEDD）及收缩末期内径（LVESD）增加,左室短轴缩短率（FS）明显降低（P〈0.01）;病理学结果证实符合心肌病样改变。ADR-DCM组大鼠左室心肌中EMMPRIN蛋白表达较CON组明显升高（P〈0.01）,MMPs明胶酶活性显著增加（P〈0.01）。结论ADR-DCM左室心肌MMPs明胶酶活性增加可能与EMMPRIN表达上调有关。

The expression of extracelinlar matrix metalloproteinases inducer is upregulated in left ventricular myocardium of adriamyein - induced dilated eardiomyopathy rats

Objective To investigate the expression of extracellular matrix metalloproteinases inducer(EMMPRIN) in the left ventricular myocardium of adriamycin-induced dilated cardiomyopathy rat.Methods 35 adult male Wistar rats were devided into two groups including the adriamycin-induced dilated cardiomyopathy rat(ADR-DCM group,n=25) and the control group(n=10).The ADR-DCM group was injected with adriamycin at a dose of 2.5 mg/kg intravenously once a week for 10 weeks,and the control groupreceived an equivalent volume of 0.9% salinealone intravenously.Echocardiographic measurements were obtained at 12 weeks after treatment.Then LV samples were collected.The pathological change was analyzed by histological hematoxylin-eosin staining.The protein expression of EMMPRIN in the left ventricular myocardium was measured by Western blot.MMP-2 and-9 gelatinolytic activity were measured by gelatin zymography.Results The cumulative mortality in ADR-DCM group was 40%.Compared to the control group,LV end-diastolicdiameter(LVEDD) and LV end systolic diameter(LVESD) were significantly increased in ADR-DCM group(all P<0.01).FS was significantly reduced in ADR-DCM group(P<0.01).The pathological examination was consistent with histological changes of cardiomypathy.In comparison to the control group rats,the protein level of LV myocardial EMMPRIN was upregulated in the ADR-DCM group rat(P<0.01).LV myocardial MMP-2 and-9 gelatinolytic activity were increased significantly in ADR-DCM group(both P<0.01).Conclusion The expression of EMMPRIN is upregulated in left ventricular myocardium of adriamycin-induced dilated cardiomyopathy rats,which could result in the increase of left ventricular myocardial MMP-2 and-9 gelatinolytic activity.