中华老年医学杂志
中華老年醫學雜誌
중화노년의학잡지
Chinese Journal of Geriatrics
2013年
8期
882-885
,共4页
孔朝红%刘煜敏%朱江%周绍霞%李芹
孔朝紅%劉煜敏%硃江%週紹霞%李芹
공조홍%류욱민%주강%주소하%리근
粒细胞集落刺激因子%脑缺血%血管内皮生长因子类
粒細胞集落刺激因子%腦缺血%血管內皮生長因子類
립세포집락자격인자%뇌결혈%혈관내피생장인자류
Granulocyte colony-stimulating factor%Brain ischemia%Vascular endothelial growth factors
目的 观察粒细胞集落刺激因子(G-CSF)对慢性脑缺血大鼠行为学的影响,并探讨其可能的机制.方法 制备大鼠慢性脑缺血双侧颈动脉结扎(2-VO)模型,随机分为假手术对照组和手术组,将手术组大鼠随机分为粒细胞集落刺激因子(G-CSF)组和磷酸盐缓冲液(PBS)组.术后6周G-CSF组经颈外静脉注射G-CSF(10 mg/L,1 ml· kg-1·d-1),PBS组给予PBS(1 ml/kg),每间隔24 h干预1次,共3次,假手术对照组仅分离出双侧颈外静脉,不干预.术后8周行Morris水迷宫评价大鼠空间学习记忆功能变化,同时通过观察缺血区细胞增生情况、激光共聚焦三维血管成像、缺血区神经细胞的凋亡和形态学变化以及血管内皮生长因子(VEGF)浓度等探讨其可能的机制.结果 水迷宫检测结果显示,训练第2天至第5天大鼠逃避潜伏期G-CSF组明显短于PBS组(均P＜0.05)；第1象限游泳时间G-CSF组明显长于PBS组(P＜0.05).缺血脑组织内的BrdU阳性细胞数G-CSF组(27.7±4.76)个/视野,明显高于PBS对照组(10.4±3.7)个/视野(P=0.030).脑血管共聚焦检测结果显示,G-CSF组与PBS组比较,毛细血管直径明显变小[(2.90±0.20) μm与(3.45±0.26)μm,P=0.020],同源组织缺血边界地区的分支点数目显著增加[(207.82±10.73)个/0.002mm3与(162.10±9.31)个/0.002 mm3,P=0.005],微血管总面积显著增加[(86498±2896)μm2/0.002mm3与(73976±3826)μm2/0.002mm3,P=0.003].凋亡检测结果显示,G-CSF组细胞凋亡数目(32.10±6.70)个/视野,较PBS组(56.30±11.20)个/视野明显减少(F=11.89,P=0.043).电镜下形态学观察结果显示,G-CSF组大鼠的细胞间隙炎性水肿明显减轻；G-CSF组大鼠血浆VEGF水平(58.81±6.61) ng/L,较PBS组(20.81±4.35) ng/L增加(P=0.025).结论 G-CSF可显著改善慢性脑缺血大鼠的空间学习记忆能力,其机制可能与VEGF的神经血管保护作用有关,其在缺血性脑血管病治疗中有较大的应用前景.
目的 觀察粒細胞集落刺激因子(G-CSF)對慢性腦缺血大鼠行為學的影響,併探討其可能的機製.方法 製備大鼠慢性腦缺血雙側頸動脈結扎(2-VO)模型,隨機分為假手術對照組和手術組,將手術組大鼠隨機分為粒細胞集落刺激因子(G-CSF)組和燐痠鹽緩遲液(PBS)組.術後6週G-CSF組經頸外靜脈註射G-CSF(10 mg/L,1 ml· kg-1·d-1),PBS組給予PBS(1 ml/kg),每間隔24 h榦預1次,共3次,假手術對照組僅分離齣雙側頸外靜脈,不榦預.術後8週行Morris水迷宮評價大鼠空間學習記憶功能變化,同時通過觀察缺血區細胞增生情況、激光共聚焦三維血管成像、缺血區神經細胞的凋亡和形態學變化以及血管內皮生長因子(VEGF)濃度等探討其可能的機製.結果 水迷宮檢測結果顯示,訓練第2天至第5天大鼠逃避潛伏期G-CSF組明顯短于PBS組(均P＜0.05)；第1象限遊泳時間G-CSF組明顯長于PBS組(P＜0.05).缺血腦組織內的BrdU暘性細胞數G-CSF組(27.7±4.76)箇/視野,明顯高于PBS對照組(10.4±3.7)箇/視野(P=0.030).腦血管共聚焦檢測結果顯示,G-CSF組與PBS組比較,毛細血管直徑明顯變小[(2.90±0.20) μm與(3.45±0.26)μm,P=0.020],同源組織缺血邊界地區的分支點數目顯著增加[(207.82±10.73)箇/0.002mm3與(162.10±9.31)箇/0.002 mm3,P=0.005],微血管總麵積顯著增加[(86498±2896)μm2/0.002mm3與(73976±3826)μm2/0.002mm3,P=0.003].凋亡檢測結果顯示,G-CSF組細胞凋亡數目(32.10±6.70)箇/視野,較PBS組(56.30±11.20)箇/視野明顯減少(F=11.89,P=0.043).電鏡下形態學觀察結果顯示,G-CSF組大鼠的細胞間隙炎性水腫明顯減輕；G-CSF組大鼠血漿VEGF水平(58.81±6.61) ng/L,較PBS組(20.81±4.35) ng/L增加(P=0.025).結論 G-CSF可顯著改善慢性腦缺血大鼠的空間學習記憶能力,其機製可能與VEGF的神經血管保護作用有關,其在缺血性腦血管病治療中有較大的應用前景.
목적 관찰립세포집락자격인자(G-CSF)대만성뇌결혈대서행위학적영향,병탐토기가능적궤제.방법 제비대서만성뇌결혈쌍측경동맥결찰(2-VO)모형,수궤분위가수술대조조화수술조,장수술조대서수궤분위립세포집락자격인자(G-CSF)조화린산염완충액(PBS)조.술후6주G-CSF조경경외정맥주사G-CSF(10 mg/L,1 ml· kg-1·d-1),PBS조급여PBS(1 ml/kg),매간격24 h간예1차,공3차,가수술대조조부분리출쌍측경외정맥,불간예.술후8주행Morris수미궁평개대서공간학습기억공능변화,동시통과관찰결혈구세포증생정황、격광공취초삼유혈관성상、결혈구신경세포적조망화형태학변화이급혈관내피생장인자(VEGF)농도등탐토기가능적궤제.결과 수미궁검측결과현시,훈련제2천지제5천대서도피잠복기G-CSF조명현단우PBS조(균P＜0.05)；제1상한유영시간G-CSF조명현장우PBS조(P＜0.05).결혈뇌조직내적BrdU양성세포수G-CSF조(27.7±4.76)개/시야,명현고우PBS대조조(10.4±3.7)개/시야(P=0.030).뇌혈관공취초검측결과현시,G-CSF조여PBS조비교,모세혈관직경명현변소[(2.90±0.20) μm여(3.45±0.26)μm,P=0.020],동원조직결혈변계지구적분지점수목현저증가[(207.82±10.73)개/0.002mm3여(162.10±9.31)개/0.002 mm3,P=0.005],미혈관총면적현저증가[(86498±2896)μm2/0.002mm3여(73976±3826)μm2/0.002mm3,P=0.003].조망검측결과현시,G-CSF조세포조망수목(32.10±6.70)개/시야,교PBS조(56.30±11.20)개/시야명현감소(F=11.89,P=0.043).전경하형태학관찰결과현시,G-CSF조대서적세포간극염성수종명현감경；G-CSF조대서혈장VEGF수평(58.81±6.61) ng/L,교PBS조(20.81±4.35) ng/L증가(P=0.025).결론 G-CSF가현저개선만성뇌결혈대서적공간학습기억능력,기궤제가능여VEGF적신경혈관보호작용유관,기재결혈성뇌혈관병치료중유교대적응용전경.
Objective To explore the effects of granulocyte colony stimulating factor (G-CSF)on chronic cerebral ischemia in rats,and its possible mechanism.Methods Chronic cerebral ischemia (2-VO) model was prepared and bilateral external jugular veins were isolated.A total of 30 rats were divided into 2 groups at random sham group (received no intervention,n=15) and operative group (received G-CSF or PBS through external jugular vein injection,n=15).At 6 weeks after operation,the rats in operative group were divided into G--CSF group (received G-CSF 10 mg/L,1 ml · kg-1 · d-1,1 times every 24 h for,3 times) and PBS control group (received PBS 10 mg/L,1 ml ·kg 1 · d-11,1 times every 24 h for 3 times).At 8 weeks after the operation,morris water maze was carried out to evaluate the learning and memory ability of the rats.The cell proliferation,threedimensional vascular distribution,ischemic neuronal apoptosis,cell morphological changes in ischemic area and the plasma VEGF levels were detected to explore the possible mechanisms.Results In morris water maze,escape latency at the 2rd to 5th day were significantly lower in G-CSF group than the PBS group (all P＜0.05).The swimming time spent in the first quadrant in G-CSF group was significantly longer than the PBS group (P＜0.05).There was a significant difference in the number of BrdU positive cells in the ischemical area between the G-CSF group and the control group [(27.7±4.76) vs.(10.4 ± 3.7),P =0.030).Three-dimensional quantitative measurements of vascular structure showed that the capillary diameters was smaller in the G-CSF group than in the PBS group [(2.90±0.20) μm vs.(3.45±0.26) μm,P=0.020] and the number of branch points in the boundary regions of ischemia had a significant difference in the G-CSF group compared with the control group [(207.82±10.73) /0.002 mm3 vs.(162.10±9.31) /0.002mm3,P=0.005].Threedimensional cerebral vessel surface area in the ipsilateral hemisphere was increased in the G-CSF group compared with the PBS group [(86498±2896) μm2/0.002 mm3vs.(73976±3826) μm2/0.002 mm3,P=0.003].The number of apoptotic cells in G-CSF group was decreased compared with the PBS group [(32.10±6.70) vs.(56.30±11.20),F=11.89,P=0.043].The electron microscope morphological observations showed inflammatory edema in intercellular gap was significantly reduced in the G-CSF group compared with the PBS group.The level of plasma VEGF was significantly increased in the G-CSF group compared with the PBS group [(58.81±6.61) ng/L vs.(20.81±4.35)ng/L,P=0.025].Conclusions G--CSF can improve the learning and memory ability in the chronic cerebral ischemic rats,and its possible mechanism might involve the nerve protection and the vascular regeneration associated with the VEGF.There is a great prospect for G-CSF in the therapy of chronic cerebral ischemic disease.
