CAJ | 학술논문

目的探讨经鼻靶向中枢导入重组人粒细胞集落刺激因子(rhG-CSF)对脑梗死大鼠皮层Fas配体(FasL)和血红素氧合酶-1(HO-1)表达的影响. 方法将60只大鼠按随机数字表法分为正常组、假手术组、脑梗死组、脑梗死+皮下注射rhG-CSF组、脑梗死+经鼻导入生理盐水组、脑梗死+经鼻导入rhG-CSF组.线栓法制作大鼠可逆性大脑中动脉阻塞(MCAO)模型,2 h后再灌注.于MCAO模型制作成功后1 d、3 d制备脑组织冠状冰冻切片,用免疫荧光染色检测FasL和HO-1在缺血半暗带皮层的表达,激光共聚焦显微镜采集图像并计数阳性细胞数. 结果正常组和假手术组大鼠脑组织中见极少量FasL和HO-1阳性细胞,两组比较差异无统计学意义(P>0.05).脑梗死组大鼠FasL和HO-1阳性细胞数明显增加(1 d时较3 d时高),表达区域主要为缺血半暗带皮层,与脑梗死+经鼻导入生理盐水组比较差异无统计学意义(P>0.05).经鼻给予rhG-CSF治疗后脑梗死大鼠脑组织内FasL阳性细胞表达下降,HO-1阳性细胞表达进一步上调,与脑梗死+皮下注射rhG-CSF组大鼠比较差异有统计学意义(P<0.05). 结论经鼻靶向中枢导入rhG-CSF可以通过降低FasL、上调HO-1表达抑制脑梗死大鼠缺血半暗带皮层神经元凋亡,参与脑保护机制.
목적 탐토경비파향중추도입중조인립세포집락자격인자(rhG-CSF)대뇌경사대서피층Fas배체(FasL)화혈홍소양합매-1(HO-1)표체적영향. 방법장60지대서안수궤수자표법분위정상조、가수술조、뇌경사조、뇌경사+피하주사rhG-CSF조、뇌경사+경비도입생리염수조、뇌경사+경비도입rhG-CSF조.선전법제작대서가역성대뇌중동맥조새(MCAO)모형,2 h후재관주.우MCAO모형제작성공후1 d、3 d제비뇌조직관상빙동절편,용면역형광염색검측FasL화HO-1재결혈반암대피층적표체,격광공취초현미경채집도상병계수양성세포수. 결과정상조화가수술조대서뇌조직중견겁소량FasL화HO-1양성세포,량조비교차이무통계학의의(P>0.05).뇌경사조대서FasL화HO-1양성세포수명현증가(1 d시교3 d시고),표체구역주요위결혈반암대피층,여뇌경사+경비도입생리염수조비교차이무통계학의의(P>0.05).경비급여rhG-CSF치료후뇌경사대서뇌조직내FasL양성세포표체하강,HO-1양성세포표체진일보상조,여뇌경사+피하주사rhG-CSF조대서비교차이유통계학의의(P<0.05). 결론경비파향중추도입rhG-CSF가이통과강저FasL、상조HO-1표체억제뇌경사대서결혈반암대피층신경원조망,삼여뇌보호궤제.
Objective To investigate the effect of intranasal administration of recombinant human granulocyte colony stimulating factor (rhG-CSF) on Fas ligand (FasL) and hemeoxygenase-1 (HO-1) expressions in the cortical brain tissue of rats with ischemic cerebral infarction. Methods Sixty adult male SD rats were randomly assigned into 6 groups, namely the normal control group (n=6), sham-operated group (n=6), middle cerebral artery occlusion (MCAO) group (model group), and another 3 MCAO groups with intranasal administration of normal saline (NS), subcutaneous rhG-CSF injection, and intranasai rhG-CSF administration, respectively. In the 4 MCAO groups (n=12), the rats were subjected to temporary middle cerebral artery occlusion (MCAO) for 2 h, and on the next and third days following MCAO, 6 rats from each group were sacrificed and the coronal frozen sections of the brain tissue were prepared to detect the expressions of FasL and HO-1 in the ischemic penumbra using immunohistochernical staining. Laser scanning confocal microscopy was performed to observe the amount of positive cells in the ischemic penumbra. Results In both of the normal control and sham-operated groups, only a small number of FasL- and HO-l-positive cells were found in the brain of the rats (P>0.05). In MCAO model group, the expressions of FasL and HO-1 increased obviously, which were higher on day 1 than on day 3 and located mainly in the ischemic penumbra, and saline administration did not cause obvious changes in their expressions (P>0.05). rhG-CSF treatment, administered either intranasally or subcutaneously, resulted in significantly lowered FasL expression and increased HO-1 expression, but the changes were more obvious in intranasal rhG-CSF group (P<0.05). Conclusion Intranasal rhG-CSF administration offers brain protection by inhibiting FasL expression and up-regulating HO-1 expression in rats with cerebral ischemia.