Robo4敲除对急性心肌梗死大鼠心功能的影响
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摘要
目的探讨Robo4敲除对大鼠急性心肌梗死后心功能的影响。方法采用结扎左冠状动脉主干方法复制大鼠急性心肌梗死模型,分为Robo4敲除大鼠假手术组(Robo4 sham)、SD大鼠假手术组(SD sham)、Robo4敲除大鼠心肌梗死组(Robo4 MI)和SD大鼠心肌梗死组(SD MI)。14 d后通过右颈总动脉插管法分析大鼠心功能的变化。结果两组假手术组相比,心功能无明显变化。与SD sham组相比,SD MI组左室舒张末压(LVEDP)显著升高,左室最大收缩速率(+dp/dtmax)和左室最大舒张速率(-dp/dtmax)显著下降。与SD MI组相比,Robo4 MI组LVEDP显著下降,+dp/dtmax、-dp/dtmax显著升高。结论心肌梗死14 d后大鼠心功能下降,但Robo4敲除可以改善大鼠心功能。
Objective To investigate the effects of Robo4 knockout on rats' cardiac function after acute myocardial infarction.Methods Rat models of acute myocardial infarction were replicated by ligation of left coronary artery trunk, and they were divided into Robo4 knockout rat sham operation group(Robo4 sham), SD rat sham operation group(SD sham), Robo4 knockout rat myocardial infarction group(Robo4 MI) and SD rat myocardial infarction group(SD MI). the cardiac function was measured 14 days after intubation of the right common carotid artery.Results The cardiac function had no significantly difference between Robo4 sham group and SD sham group(P < 0.05).Compared with the SD sham group, left ventricular end-diastolic pressure(LVEDP) was significantly increased in the SD MI group, and the left ventricular maximum contraction rate(+dp/dtmax) and left ventricular maximum relaxation rate(-dp/dtmax) were significantly decreased(all P < 0.05). Compared with the SD MI group, the LVODP of the Robo4 MI group decreased significantly, and +dp/dtmax and-dp/dtmax increased significantly(all P < 0.05).Conclusions Cardiac function decreased after 14 days of myocardial infarction, but it improved by Robo4 knockout.
Objective To investigate the effects of Robo4 knockout on rats' cardiac function after acute myocardial infarction.Methods Rat models of acute myocardial infarction were replicated by ligation of left coronary artery trunk, and they were divided into Robo4 knockout rat sham operation group(Robo4 sham), SD rat sham operation group(SD sham), Robo4 knockout rat myocardial infarction group(Robo4 MI) and SD rat myocardial infarction group(SD MI). the cardiac function was measured 14 days after intubation of the right common carotid artery.Results The cardiac function had no significantly difference between Robo4 sham group and SD sham group(P < 0.05).Compared with the SD sham group, left ventricular end-diastolic pressure(LVEDP) was significantly increased in the SD MI group, and the left ventricular maximum contraction rate(+dp/dtmax) and left ventricular maximum relaxation rate(-dp/dtmax) were significantly decreased(all P < 0.05). Compared with the SD MI group, the LVODP of the Robo4 MI group decreased significantly, and +dp/dtmax and-dp/dtmax increased significantly(all P < 0.05).Conclusions Cardiac function decreased after 14 days of myocardial infarction, but it improved by Robo4 knockout.
引文
[1] Jones CA, London NR, Chen H, et al. Robo4 stabilizes the vascular network by inhibiting pathologic angiogenesis and endothelial hy perpermeability[J]. Nat Med 2008,14:448-453.
[2]陈伟伟,高润霖,刘力生,等.《中国心血管病报告2017概要》[J].中国循环杂志,2018,33:1-8.
[3] Gao XM, Dart AM, Dewar E, et al. Serial echocardiographic assessment of left ventricular dimensions and function after myocardial infarction in mice[J]. Cardiovasc Res,2000,45(2):330-338.
[4]左红波,李辞霞,郭志坤.大鼠心肌梗死后心功能变化与新生血管的关系[J].解剖学报,2014,45(6):835-840.
[5] Jin X, Shin YJ, Riew TR, et al. Increased Expression of Slit2 and its Robo Receptors During Astroglial Scar Formation After Transient Focal Cerebral Ischemia in Rats[J].Neurochem Res,2016,41(12):3373-3385.
[6] Abdelsaid M, Coucha M, Hafez S, et al. Enhanced? VEGF signalling mediates cerebral neovascularisation via downregulation of guidanceprotein ROBO4 in a rat model of diabetes[J].Diabetoloqia,2017,60(4):740-750.
[7] Burke-Gaffney A, Svermova T, Mumby S, et al. Raised plasma robo4 and cardiac surgery-associated acute kidney injury[J]. Plos One,2014,9(10):e111459.
[8]陈桂秀,王浩宇,刘涛,等. Slit2/Robo4信号通路对小鼠心肌微血管内皮细胞增殖和迁移的影响[J].中华心血管病杂志,2013,41(12):1034-1039.
[9] Marlow R, Binnewies M, Sorensen LK, et al. Vascular Robo4 restricts proangiogenic VEGF signaling in breast[J].Proc Natl Acad Sci U S A,2010,107:10520-10525.
[2]陈伟伟,高润霖,刘力生,等.《中国心血管病报告2017概要》[J].中国循环杂志,2018,33:1-8.
[3] Gao XM, Dart AM, Dewar E, et al. Serial echocardiographic assessment of left ventricular dimensions and function after myocardial infarction in mice[J]. Cardiovasc Res,2000,45(2):330-338.
[4]左红波,李辞霞,郭志坤.大鼠心肌梗死后心功能变化与新生血管的关系[J].解剖学报,2014,45(6):835-840.
[5] Jin X, Shin YJ, Riew TR, et al. Increased Expression of Slit2 and its Robo Receptors During Astroglial Scar Formation After Transient Focal Cerebral Ischemia in Rats[J].Neurochem Res,2016,41(12):3373-3385.
[6] Abdelsaid M, Coucha M, Hafez S, et al. Enhanced? VEGF signalling mediates cerebral neovascularisation via downregulation of guidanceprotein ROBO4 in a rat model of diabetes[J].Diabetoloqia,2017,60(4):740-750.
[7] Burke-Gaffney A, Svermova T, Mumby S, et al. Raised plasma robo4 and cardiac surgery-associated acute kidney injury[J]. Plos One,2014,9(10):e111459.
[8]陈桂秀,王浩宇,刘涛,等. Slit2/Robo4信号通路对小鼠心肌微血管内皮细胞增殖和迁移的影响[J].中华心血管病杂志,2013,41(12):1034-1039.
[9] Marlow R, Binnewies M, Sorensen LK, et al. Vascular Robo4 restricts proangiogenic VEGF signaling in breast[J].Proc Natl Acad Sci U S A,2010,107:10520-10525.