摘要
背景与目的:开放血脑屏障将为胶质瘤的综合治疗提供新的希望,本研究观察C6脑胶质瘤不同区域血-脑屏障(BBB)的通透性的变化、超微结构特征及紧密连接蛋白claudin-5的表达变化。方法:雄性SD大鼠,随机分为对照组和荷瘤组,采用立体定向方法在大鼠右侧尾状核接种C6细胞建立大鼠C6胶质瘤模型,于建模后第20天取肿瘤、肿瘤临近处(brain adjacent to tumor,BAT)即距肿瘤边界2mm以内及肿瘤远隔处(brain dis-tant to tumor,BDT)即2mm以外的大脑半球脑皮质3个部位的脑组织和对照鼠右侧尾状核正常脑组织,采用外源性硝酸镧透射电镜示踪法,观察BBB/BBTB超微结构特征;免疫组化法观察紧密连接蛋白claudin-5在正常鼠和荷瘤鼠各部位的表达变化。结果:(1)肿瘤处可见La3+通过血管内皮细胞的紧密连接渗透至血管腔外及脑间质裂隙内,BAT部分见La3+渗出至局部基底膜,大部分分布在血管腔内,而BDT及对照组正常脑组织La3+分布在血管腔内,血管内皮细胞紧密连接结构完整,基底膜呈线状连续,脑血管内皮细胞浆均未见La3+。(2)claudin-5在BDT与对照组脑组织表达丰富、连续;肿瘤处表达减弱,沿血管呈间断表达;BAT较正常脑组织表达下降,但仍呈连续状态。结论:正常脑组织血脑屏障稳定,通透性最低;肿瘤的周边存在不同程度的屏障;C6胶质瘤细胞的直接浸润可以降低内皮细胞紧密连接蛋白claudin-5,可能是诱导紧密连接破坏导致BBTB通透性增高的重要原因。
BACKGROUND ＆ OBJECTIVE： The Opening of blood-brain barrier （BBB） could be one of the most promising combined strategies against gliomas. To investigate the change in BBB permeability and ultrastructure of microvessle in the different regions of cerebral C6 glioma and to investigate the tight junction protein expression of claudin-5 in these regions. METHODS： Male SD rats were randomly divided into control group and intracranial C6 glioma group. The models of C6 glioma were established by stereotaxical injection of C6 glioma cells into the right caudate nuclei in male SD rats. The rats with intracranial C6 glioma were sacrificed on day 20 of C6 and the samples were chosen from tumor tissue regions including BAT （tissues within 2 mm to the border of the tumor）, BDT （cortical tissues more than 2 mm away from tumor border） respectively The normal right caudate nuclei tissues of the control group were also analyzed.The ultrastructures of BBB and BBTB in the interested regions were observed by lanthanum nitrate （La^3 ＋ ）-tracingand a transmission electron microscope. Immunohistochemical methods were used to detect the tight junction protein expression of claudin-5. RESULTS： （1） In the tumor region, La^3＋ crossed the tight junctions of vascular endothelium cells and was observed in the tissues out of the vascular cavities. In BAT, La^3＋ extravasated to the basement membrane （BM） of the capillaries. In the normal cerebral areas, La^3＋ appeared only within the vascular cavities and the structure of tight junction is integrated. The BM of microvessels in the glioma was continued and compact. No La^3＋ was observed in the cytoplasm of the endothelium cells of the cerebral microvessel in all the observed tissues. （2） In the BDT and non-tumor brain tissues, overexpression of claudin-5 was observed.The expression of the tumors is low, which was discontinuously observed along vascular cavities. In contrast with the normal tissues, the expression is lower in BAT, but still can be localized continuously. CONCLUSION： The BBB of normal brain tissues is intact, which the permeability is lowest. There is some extent barrier in the border of glioma. The expression of tight junction protein claudin-5 decreased in the regions with glioma cell invasion, which may be the important reason for opening tight junctions and resulting in the enhancement of BBTB permeability in C6 glioma.
出处
《中国神经肿瘤杂志》
2008年第3期184-188,共5页
Chinese Journal of Neuro-Oncology
