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目的:研究~(192)铱脑胶质瘤间质内放疗所产生的生物学反应及对周边正常脑组织的影响,为临床应用提供可靠的理论依据。方法:采用动物实验与病理学观察相结合方法。(1)制备 G422胶质母细胞瘤株皮下荷瘤小鼠模型,接种后14天,待肿瘤生长至肉眼可见,将小鼠分为三组:2.5Gy、10Gy 照射组和不照射的对照组,每组8只,观察肿瘤生长抑制、组织学改变;(2)制备 C6胶质母细胞瘤脑内荷瘤大鼠模型,在颅内接种 C6细胞后14天,将大鼠分为三组:2.5Gy、10Gy 照射组和不照射的对照组(每组8只),观察指标为生长期延长的肿瘤组织学变化。结果:(1)G422皮下荷瘤照射6、14天后,两照射组肿瘤平均体积明显缩小,照射8h 后25Gy组有散在局灶性坏死,边缘区核胞浓集或破碎,10Gy 组以上变化更明显。电镜下2.5Gy 细胞核被挤压一侧,细胞器肿胀,胞浆内包涵体较多。10Gy 组见大量各期坏死瘤细胞。照射8h,坏死面积对照组8.4%,2.5Gy 组18.2%.10Gy 组32.7%;照射14天时,三组分别为30.6%、73.3%和75.3%。(2)C6脑内荷瘤:照射组的生存期明显延长,2.5Gy 组又较10Gy 组显著延长。光镜下:2.5Gy 组瘤组织内坏死、出血,边缘部分核浓缩和破坏。中心区结构破坏,仅残留胞膜;10Gy 组瘤内大片坏死和出血,坏死边缘小血管扩张。电镜下:2.5Gy 组见坏死瘤细胞,胞核被挤压一侧,细胞器肿胀,胞浆包涵体较多;10Gy 组见大量各期坏死瘤细胞。坏死面积对照组37.1%,2.5Gy 组80.5%,10Gy 组为61.2%。结论:(1)G422皮下荷瘤鼠模型和 G6脑内荷瘤鼠模型的制备,结果可靠,重复性好,肿瘤生长符合实验要求,可达到观察肿瘤经放疗后生长抑制的目的,是理想的间质内放疗生物学研究的动物模型;(2)本实验证实,不论皮下荷瘤还是脑内荷瘤,经瘤间质内照射治疗,可引发小鼠不同程度的生长期延长。组织学观察证明,不同剂量瘤间质内插入~(192)铱放射源可引起肿瘤细胞的凋亡及坏死性变化,2.5Gy 组为80.5%,疗效最好,而10Gy 组因引起瘤内大片坏死,周边正常脑组织也有一定程度的血管扩张、充血和脑水肿反应,因此选用分割的低剂量瘤内间质放疗法是治疗脑内恶性肿瘤的有效方法。
OBJECTIVE: To study the biological response of ~ (192) iridium glioma interstitial radiotherapy and its effect on peripheral normal brain tissue, so as to provide a reliable theoretical basis for clinical application. Methods: The combination of animal experiments and pathological observation methods. (1) A subcutaneous tumor-bearing mouse model of G422 glioblastoma was prepared. After 14 days of inoculation, the mice were divided into three groups: 2.5Gy, 10Gy irradiation group and non-irradiated control group , Each group of 8, observation of tumor growth inhibition, histological changes; (2) Preparation of C6 glioblastoma brain tumor-bearing rat model, 14 days after intracerebral inoculation of C6 cells, the rats were divided into three groups : 2.5Gy, 10Gy irradiation group and non-irradiated control group (8 rats in each group). The observation index was the histological change of the tumor with prolonged growth period. Results: (1) After 6 and 14 days of G422 subcutaneous tumor irradiation, the mean volume of tumors in the two irradiation groups was significantly reduced. After 8 hours of irradiation, focal necrosis was scattered in the 25Gy group and the nuclei in the marginal zone were concentrated or broken. obvious. Under electron microscope, 2.5Gy nucleus was squeezed side, organelles swollen, cytoplasmic inclusion bodies more. 10Gy group see a large number of necrotic tumor cells. 8h after irradiation, 8.4% in the necrotic area control group, 18.2% in the 2.5Gy group and 32.7% in the 10Gy group. The levels in the three groups were 30.6%, 73.3% and 75.3% respectively at 14 days of irradiation. (2) C6 brain tumor-bearing: irradiation group significantly prolonged survival, 2.5Gy group was significantly longer than the 10Gy group. Under light microscope: Necrosis of 2.5Gy group tumor, hemorrhage, the edge part of the nuclear condensation and destruction. Structural damage in the central area, leaving only the membrane; 10Gy group tumor necrosis and hemorrhage, small blood vessels at the edge of necrosis dilatation. Electron microscope: 2.5Gy group necrotic tumor cells, the nucleus is squeezed side, organelles swelling, cytoplasmic inclusion bodies more; 10Gy group see a large number of necrotic tumor cells. The area of necrosis was 37.1% in the control group, 80.5% in the 2.5Gy group and 61.2% in the 10Gy group. Conclusion: (1) The G422 subcutaneous tumor-bearing mouse model and G6 intracerebral tumor-bearing mouse model have reliable results and good repeatability. The tumor growth meets the experimental requirements and can be observed to observe the growth inhibition of tumor after radiotherapy, which is ideal (2) This experiment confirmed that, regardless of subcutaneous tumor or brain tumor, tumor interstitial irradiation therapy, can cause mice to varying degrees of growth period. Histological observation showed that ~ (192) iridium radioactive sources were inserted into the interstitial of different doses to induce the apoptosis and necrosis of tumor cells. The 2.5Gy group was 80.5% with the best curative effect, while the 10Gy group Necrosis, the surrounding normal brain tissue also has a certain degree of vasodilation, congestion and brain edema response, so the selection of low-dose intra-tumor interstitial radiotherapy is an effective method of treatment of intracranial malignant tumors.