粒细胞集落刺激因子经鼻给药对大鼠脑梗死后的促血管新生作用

Promotive effect of neovascularization on rats with cerebral infarction by intranasal administration of granulocyte colony-stimulating factor

目的探讨经鼻腔给予粒细胞集落刺激因子（G．CSF）对急性脑梗死后血管新生的影响。方法sD大鼠采取线栓法制作大脑中动脉闭塞模型（MCAO），按照投币法（随机数字表示法）将Sprague．Dawley大鼠随机分为假手术组、模型对照组、鼻腔给生理盐水组（INNS组）、皮下给药组（IHG．CSF组）、鼻腔给药组（ING—CSF）组。再灌注后72h对各组大鼠进行神经行为学评分，通过TTC染色测量脑梗死体积，用荧光免疫法检测血管内皮生长因子在脑内的表达并计数脑内新生血管密度。结果在脑缺血72h点ING—CSF组的神经功能评分[（3．90＋1．65）分]与IHG—CSF组[（10．55＋2．19）分]相比有显著改善，差异有统计学意义（P〈0．01）；ING-CSF组的脑梗死体积[（20．01±3．30）％]明显减小，与IHG-CSF组[（33．48±4．49）％]相比有统计学意义（P〈0．01），INNS组[（60．20＋7．72）％]与模型组[（61．496．41）％]相比差异无统计学意义（尸〉0．05）；ING-CSF组大鼠脑内VEGF表达（荧光密度）为33．352．79，较模型对照组（21．48_＋2．65）、INNS组（21．482．65）、假手术组（5．811．08）、IHG-CSF组（25．012．09）明显增加，微血管密度显著增加（P〈O．06）。结论经鼻给予G-CSF对于脑梗死的治疗具有显著的神经保护作用，并可显著促进血管新生。

Objective To study the promotive effect of neovascularization on rats with cerebral infarction by nasal administration of granulocyte colony-stimulating factor. Methods A blinded, vehicle-controlled study of ING-CSF and IHG-CSF administration was performed by intraluminal middle cerebral artery occlusion （MCAO） model.All Sprague-Dawley rats were randomly divided into sham-operation group, model group,INNS group, IHG- CSF group and ING-CSF group.The neurologic behavioral tests were assessed after reperfusiou 72 h.After 72 h of MCAO, the brains of rats were stainned with TYC and the infarcted volume was calculated by computer image anal- ysis. The expression of vascular endothelial growth factor （VEGF） in the brain was determined by immune-histo- chemistry.The density of angiogenesis in the brain was counted under fluorescence microscope. Results The score of neurological function of ING-CSF group （3.90~ 1.65 ）was improved significantly compared with the IHG-CSF group （10.55~2.19） at the point of 72 h after cerebral infarction （P〈0.O1）.The cerebral infarct volume of ING-CSF group（ （20.01~3.29） % ） was reduced evidently compared with the IHG-CSF group（ （33.48＋4.49） % ） at 72 h （P〈 0.01 ） ;while the cerebral infarct volume of INNS group（（60.20＋7.72） % ）was not markedly different compared with the model group （ （ 61.49 ＋ 6.41 ） % ） at 72 h （P〉 0.05 ）. The expression of VEGF in the brains of ING-CSF group was significantly higher than other groups at 72 h. Conclusion Intranasal administration G-CSF can im- prove neurological function and vascular angiogenesis in rats following MCAO.