Robo4敲除促进大鼠缺血心肌微血管生成
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摘要
目的探讨Robo4敲除对大鼠急性心肌梗死后缺血心肌微血管生成的影响。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天后提取大鼠MI边缘区心肌组织,VWF8免疫组织化学染色,检测微血管生成密度(MVD)。结果两假手术组间MI边缘区MVD无明显变化[(2.27±0.53)个比(1.89±0.34)个,P>0.05]。与SD sham组相比,SD MI组MI边缘区MVD显著增加[(16.63±3.13)个比(1.89±0.34)个,P<0.01]。与SD MI组相比,Robo4 MI组MI边缘区MVD显著增加[(22.49±3.05)个比(16.63±3.13)个,P<0.05]。结论大鼠急性心肌梗死14天后缺血心肌微血管生成增加,且Robo4敲除可以促进缺血心肌微血管生成。
Objective To investigate the effects of Robo4 knockout on rats' myocardial neovascularization after acute myocardial infarction.Methods Use left main coronary artery ligation to copy acute myocardial infarction rats models,which were randomly divided into Robo4 sham group,SD sham group,Robo4 MI group and SD MI group.In 14 days after ligation of the left main coronary artery,cardiac muscle tissue were extracted from MI fringe area in rats,microvascular density(MVD) was measured by VWF8 immunohistochemistry.Results The MVD had no significantly difference between Robo4 sham group and SD sham group(2.27±0.53 vs 1.89±0.34,P>0.05).Compared with SD sham group,MVD was effectively increased in SD MI group(16.63±3.13 vs 1.89±0.34,P<0.001).Compared with SD MI group,MVD was significantly increased in Robo4 MI group(22.49±3.05 vs 16.63±3.13,P=0.017).Conclusions Myocardial neovascularization was appeared 14 days after acute myocardial infarction,and Robo4 knockout could improve it.
Objective To investigate the effects of Robo4 knockout on rats' myocardial neovascularization after acute myocardial infarction.Methods Use left main coronary artery ligation to copy acute myocardial infarction rats models,which were randomly divided into Robo4 sham group,SD sham group,Robo4 MI group and SD MI group.In 14 days after ligation of the left main coronary artery,cardiac muscle tissue were extracted from MI fringe area in rats,microvascular density(MVD) was measured by VWF8 immunohistochemistry.Results The MVD had no significantly difference between Robo4 sham group and SD sham group(2.27±0.53 vs 1.89±0.34,P>0.05).Compared with SD sham group,MVD was effectively increased in SD MI group(16.63±3.13 vs 1.89±0.34,P<0.001).Compared with SD MI group,MVD was significantly increased in Robo4 MI group(22.49±3.05 vs 16.63±3.13,P=0.017).Conclusions Myocardial neovascularization was appeared 14 days after acute myocardial infarction,and Robo4 knockout could improve it.
引文
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[4]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.
[5]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.
[6]Marlow R,Binnewies M,Sorensen LK,et al.Vascular Robo4 restricts proangiogenic VEGF signaling in breast[J].Proc Natl Acad Sci USA,2010,107(23):10520-10525.
[7]Burke-Gaffney A,Svermova T,Mumby S,et al.Raised plasma robo4and cardiac surgery-associated acute kidney injury[J].Plos One,2014,9(10):e111459.
[8]Chen GX,Wang HY,Liu T,et al.Myocardial Slit2-Robo4 expression and impact of exogenous Slit2 on proliferation and migration of cardiac microvascular endothelial cells[J].中华心血管病杂志,2013,41(12):1034-1039.
[2]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.
[3]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.
[4]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.
[5]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.
[6]Marlow R,Binnewies M,Sorensen LK,et al.Vascular Robo4 restricts proangiogenic VEGF signaling in breast[J].Proc Natl Acad Sci USA,2010,107(23):10520-10525.
[7]Burke-Gaffney A,Svermova T,Mumby S,et al.Raised plasma robo4and cardiac surgery-associated acute kidney injury[J].Plos One,2014,9(10):e111459.
[8]Chen GX,Wang HY,Liu T,et al.Myocardial Slit2-Robo4 expression and impact of exogenous Slit2 on proliferation and migration of cardiac microvascular endothelial cells[J].中华心血管病杂志,2013,41(12):1034-1039.