Apelin-13对肾上腹主动脉缩窄诱导的心力衰竭大鼠心肌纤维化的影响

The effect of Apelin-13 on heart failure rats induced by the renal upper abdominal aortic constriction

目的观察外源性给予Apelin-13对肾上腹主动脉缩窄法诱导的心力衰竭大鼠心肌纤维化的影响。方法将40只SD雄性大鼠随机分为假手术组、模型组、低剂量Apelin-13组、高剂量Apelin-13组,每组10只。应用肾上腹主动脉缩窄法建立心力衰竭模型。低剂量Apelin-13组、高剂量Apelin-13组腹腔注射Apelin-13分别为1、10μg/(kg.d)。4周后测定各组血流动力学指标,应用ELISA法测定血清TGF-β1、BNP、MMP-2、TIMP-1水平。测量心肌胶原容积分数(CVF)。结果与假手术组相比,模型组LVESP、LV±dp/dtmax显著降低,LVEDP显著升高,P均<0.01;高剂量Apelin-13组LVESP、LV±dp/dtmax明显高于模型组,LVEDP明显低于模型组,P均<0.01。TGF-β1、BNP及TIMP-1在模型组、低剂量Apelin-13组、高剂量Apelin-13组均明显升高,MMP-2、MMP-2/TIMP-1均明显降低,P均<0.05。低剂量Apelin-13组、高剂量Apelin-13组与模型组间上述指标比较均有统计学差异(P均<0.05)。与假手术组比较,模型组、低剂量Apelin-13组、高剂量Apelin-13组CVF均明显升高(P<0.05);与模型组比较,高剂量组CVF明显降低(P<0.01)。结论外源性Apelin-13对肾上腹主动脉缩窄法诱导的心力衰竭大鼠心肌有一定保护作用,其可能通过调节MMP-2/TIMP-1,抑制细胞外基质合成,促进心肌细胞外基质成分降解,抑制心肌重构及心肌纤维化。

Objective To observe the effect of Apelin-13 on myocardial fibrosis rats induced by the renal upper abdominal aortic constriction. Methods 40 male SD rats were randomly divided into sham group, model group, low-dose Apelin-13 group and high-dose Apelin-13 group, 10 cases in each group. The renal upper abdominal aortic constriction was used to build heart failure model. Low-dose Apelin-13 group and high-dose Apelin-13 group were administered daily Apelin-13 1, 10 μg/（ kg · d） respectively by intraperitoneal injection. After 4 weeks, the hemodynamic indexes of all groups were detected, and serum levels of TGF-β, BNP, MMP-2, TIMP-1 were measured by ELISA. In addition, myocardial collagen volume fraction （CVF） was measured. Results Compared with the sham group, model group LVESP, LV ± dp / dtmax were significantly lower, LVEDP increased significantly （P 〈0.01 ） ; LVESP, LV ± dp / dtmax of high-dose Ape- lin-13 group were significantly higher than the model group, LVEDP was significantly lower than the model group （P 〈 0.01 ）. TGF-131, BNP and TIMP-1 in the model group, low-dose Apelin-13 group and high-dose Apelin-13 group were significantly higher, whereas MMP-2, MMP-2/TIMP-1 decreased significantly （P 〈0.05）. There were significant differences between model group and low-dose Apelin-13 group, high-dose Apelin-13 group. Compared with the sham group, CVF increased in model group, low-dose Apelin-13 group and high-dose Apelin-13 group （ P 〈 0.05 ） ; compared with the model group, CVF was significantly lower in high-dose Apelin-13 group （ P 〈 0.01 ）. Conclusions By the method of adjusting MMP-2/TIMP-1 to inhibit the extracellular matrix synthesis, to promote myocardial extraeellular matrix degradation and to inhibit the myocardial remodeling and myocardial fibrosis, Apelin-13 could protect myocardium of heart failure rats induced by renal upper abdominal aortic constriction.