SHR-SP脑梗死后微血管形成与星形胶质细胞的关系
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摘要
目的探讨自发性高血压大鼠(stroke-prone,spontaneously hypertensive,SHR-SP)脑梗死周围半暗区微血管形成及其构筑变化与星形胶质细胞的关系。方法建立SHR-SP脑梗死模型,从SHR-SP大鼠股静脉注入FITCdextran后在共聚焦显微镜下观察大鼠脑血管的构筑,测定微血管直径及分支数;通过免疫组织化学及免疫荧光染色法检测SHR-SP脑梗死周围半暗区GFAP、FⅧ的表达,测定其GFAP阳性细胞数、微血管密度(microvessel density,MVD),分析SHR-SP脑梗死周围半暗区星形胶质细胞数量与MVD、微血管直径及分支数的相互关系。结果 SHRSP在饮用高盐(13g/L NaCl)水溶液后第7周开始出现脑梗死;与对照组WKY比较,在SHR-SP脑梗死周围半暗区GFAP表达的阳性细胞数、MVD、微血管分支数显著升高,微血管直径显著增粗,且明显高于对侧半球相应区及非高盐饮水SHR-SP脑的相应区(P<0.01)。直线相关分析显示,GFAP表达的阳性细胞数与MVD及微血管直径及分支数呈正相关性(P<0.01)。结论高盐(13g/L NaCl)饮水可诱发SHR-SP发生脑梗死;在SHR-SP脑梗死周围半暗区,微血管形成及构筑的变化促使了星形胶质细胞的增生。
Objective To investigate the possible role of astrocytes after brain infarction in stroke-prone,spontaneously hypertensive(SHR-SP)rats and the association with angiogenesis and the architecture.Methods We maintained SHR-SP rats on high sodium water starting to accelerate the stroke onset.The 3D quantification of microvasculatures(diameter,branch number)by cofocal microscope after FITC-dextran was injected into the rats via the left femoral vein.Glial fibrillary acidic protein(GFAP)expression and microvessel density(MVD)using counting the number of factorⅧ-positive endothelial cells were evaluated by immunofluorescence and immunohistochemistry,respectively.Results Cerebral infarction occurred at week 7after high sodium water intake(13g/L NaCl)in SHR-SP group.When compared with the non-infarcted contralateral hemisphere and SHR-SP on normal sodium intake and WKY rats,GFAP expression and MVD were significantly increased,respectively,and the diameter and the branch number of vessels were decreased,respectively,in cerebral infarcts with boundary zones of SHR-SP rats(P <0.01).Linear correlation analysis showed that GFAP expression was positively correlated with MVD and the diameter and the branch number of vessels in cerebral infarcts in SHR-SP(P<0.01).Conclusion Astrocytes hyperplasia may be associated with increased regional angiogenesis and the changes of architecture in SHR-SP rats with high sodium water(13g/L NaCl)that induces focal cerebral infarcts.
Objective To investigate the possible role of astrocytes after brain infarction in stroke-prone,spontaneously hypertensive(SHR-SP)rats and the association with angiogenesis and the architecture.Methods We maintained SHR-SP rats on high sodium water starting to accelerate the stroke onset.The 3D quantification of microvasculatures(diameter,branch number)by cofocal microscope after FITC-dextran was injected into the rats via the left femoral vein.Glial fibrillary acidic protein(GFAP)expression and microvessel density(MVD)using counting the number of factorⅧ-positive endothelial cells were evaluated by immunofluorescence and immunohistochemistry,respectively.Results Cerebral infarction occurred at week 7after high sodium water intake(13g/L NaCl)in SHR-SP group.When compared with the non-infarcted contralateral hemisphere and SHR-SP on normal sodium intake and WKY rats,GFAP expression and MVD were significantly increased,respectively,and the diameter and the branch number of vessels were decreased,respectively,in cerebral infarcts with boundary zones of SHR-SP rats(P <0.01).Linear correlation analysis showed that GFAP expression was positively correlated with MVD and the diameter and the branch number of vessels in cerebral infarcts in SHR-SP(P<0.01).Conclusion Astrocytes hyperplasia may be associated with increased regional angiogenesis and the changes of architecture in SHR-SP rats with high sodium water(13g/L NaCl)that induces focal cerebral infarcts.
引文
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[13]SONG JM,NAN D,HE QH,et al.Astrocyte activation and capillary remodeling in modified bilateral common carotid artery occlusion mice[J].Microcirculation,2017,24(6):e12366.
[2]THOENE-REINEKE C,RUMSCHUESSEL K,SCHMERBACH K,et al.Prevention and intervention studies withtelmisartan,ramipril and their combination in different rat stroke models[J].PLoS One,2011,6(8):1-10.
[3]YANG Y,KIMURA-OHBA S,THOMPSON J,et al.Rodent models of vascular cognitive impairment[J].Transl Stroke Res,2016,7(5):407-414.
[4]ERGUL A,ALHUSBAN A,FAGAN SC.Angiogenesis:A harmonized target for recovery after stroke[J].Stroke,2012,43(8):2270-2274.
[5]YANG Y,KIMURA-OHBA S,THOMPSON JF,et al.Vascular tight junction disruption and angiogenesis in spontaneously hypertensive rat with neuroinflammatory white matter injury[J].Neurobiol Dis,2018,114(1):95-110.
[6]YANG XT,BI YY,FENG DF.From the vascular microenvironment toneurogenesis[J].Brain Res Bull,2011,84(1):1-7.
[7]NEVES JD,ARISTIMUNHA D,VIZUETE AF,et al.Glialassociated changes in the cerebral cortex after collagenaseinduced intracerebral hemorrhage in the rat striatum[J].Brain Res Bull,2017,134(1)55-62.
[8]程笑,杨欢,杨滢霖,等.缺血性脑卒中后星形胶质细胞信号通路变化及潜在治疗靶点研究[J].中国新药杂志,2017,26(7):749-754.
[9]DANIEL CM,THOMAS Y,MOHAMMAD MK,et al.Microvascular structure after embolic focal cerebral ischemia in the rat[J].Brain Res,2003,972(1):31-37.
[10]LUGO-HERMANDEZ E,SQUIRE A,HAGEMANN N,et al.3D visualization and quantification ofmicrovessels in the whole ischemic mouse brain using solvent-based clearing and light sheet microscopy[J].J Cerebr Blood F Met,2017,37(10):3355-3367.
[11]ZHANG X,CHEN XP,LIN JB,et al.Effect of enriched environment on angiogenesis and neurological functions in rats with focal cerebral ischemia[J].Brain Res,2017,1655(SI):176-185.
[12]YU KW,WU Y,ZHANG Q,et al.Enriched environment induces angiogenesis and improves neural function outcomes in rat stroke model[J].J Neurol Sci,2014,347(2):275-280.
[13]SONG JM,NAN D,HE QH,et al.Astrocyte activation and capillary remodeling in modified bilateral common carotid artery occlusion mice[J].Microcirculation,2017,24(6):e12366.