9L/Fischer344与C6/Wistar两种大鼠脑胶质瘤模型的比较研究

目的探讨9L/Fischer344和C6/Wistar两种大鼠脑胶质瘤模型的对比研究。方法采用立体定向技术,大鼠脑内接种定量的肿瘤细胞建立模型,比较两种模型大鼠脑内肿瘤生长情况;采用免疫组织化学方法,比较两种模型脑内肿瘤局部细胞免疫反应情况。结果(1)9L/Fischer344大鼠脑内有肿瘤持续生长,而C6/Wistar大鼠脑内早期可见肿瘤生长,但肿瘤局部有大量淋巴细胞浸润,肿瘤周边血管呈现“淋巴细胞血管套”现象,后期脑内肿瘤逐渐消退、消失,仅见残留轨迹和含褐色素沉着的吞噬细胞;(2)9L/Fischer344肿瘤局部可见CD68阳性细胞,未见CD4、CD8阳性细胞,而C6/Wistar肿瘤局部CD68阳性细胞数量明显较9L模型多(P<0.01),并可见CD4、CD8阳性的淋巴细胞。结论9L/Fischer344模型稳定性高,重复性好,肿瘤局部T淋巴细胞浸润极少,是一种较为理想的脑胶质瘤免疫治疗研究的动物模型;C6/Wistar模型脑内肿瘤不能持续生长,脑内肿瘤可自发性消退,肿瘤局部T淋巴细胞浸润明显,存在较强的细胞免疫反应,可能是肿瘤的消退的原因,该模型不适合用于胶质瘤治疗,尤其是免疫治疗的实验研究。

Comparative study of two rat brain glioma models: 9L/Fischer344 and C6/Wistar

Objective To comparatively study two rat brain glioma models: 9L/Fischer344 and C6/Wistar. Methods The syngeneic 9L/Fischer344 models a nd allogeneic C6/Wistar models were established by injecting quantitated glioma cells stereotactically into the right caudate nucleus of rats. Rats were sacrifi ced periodically to investigate the growth of brain tumors in two models. Brain tumor immunohistochemical staining for CD68, CD4 and CD8 were observed comparati vely in two models. Results (1) Constant brain-tumors growth occurred in a ll syngeneic 9L/Fischer344 model rats. But allogeneic model rats of C6/Wistar fa iled in tumor growing constantly in brain. The brain tumors of C6/Wistar existed in early period after implantation, with numerous infiltrating mononuclear cell s packing around the tumor, forming "the periarteriolar lymphocyte sheath". Tumo rs induced in Wistar rats with C6 cells almost disappeared on 20 d after implant ation. (2) Immunohiatochemical staining for CD68 molecular (macrophage/microglia marker), CD4 and CD8 molecular (T lymphocyte markers) positive cells were seen in Wistar rats extensively. Comparatively, the quantity of CD68 positive cells i n Fischer rats was lower (P<0.01) and no CD4 and CD8 positive cells were found i n Fischer rats. Conclusion The syngeneic 9L/Fischer344 model was stable an d reproductive with few tumor-infiltrating T-lymphocytes in Fischer344 rats. The 9L/Fischer344 model is available for studying brain glioma immunotherapy. Conve rsely, the allogeneic C6/Wistar model failed in tumor growing constantly in brai n. The brain tumors in C6/Wistar models can regress spontaneously. The infiltrat ion of local extensive immune cells may be the cause of tumor regression. The al logeneic C6/Wistar model is inappropriate for the investigation of brain glioma therapy, especially immunotherapy.