多西他赛联合放疗对大鼠脊髓损伤的观察

Pathology of Radiation Injury to the Rats Spinal Cord Induced by Combined Treatment with Docetaxel and Radiation

目的探讨多西他赛联合放射治疗对大鼠脊髓损伤的影响。方法将40只Wistar品系大鼠随机分为5个组,即空白组、多西他赛组、放疗组、先多西他赛后放疗组和先放疗后多西他赛组。多西他赛组单次腹腔注射多西他赛5mg/kg。放疗组、先多西他赛后放疗组和先放疗后多西他赛组采用Varian2300C/D直线加速器6MeV电子线照射大鼠胸段脊髓,照射野为2cm×4cm,5Gy/次,隔日1次,总剂量为40Gy。联合组多西他赛与照射的间隔时间为3d。照射结束后5个月,行活体灌注固定,取材,光镜和电镜观察脊髓的形态学变化。结果光镜下,放疗组和先多西他赛后放疗组白质部分坏死;先放疗后多西他赛组白质大片坏死。后2组均见胶质细胞核固缩。各组灰质内神经元和血管未见变化。电镜下,各组脊髓髓鞘改变程度不一。放疗组脊髓髓鞘板层结构水肿、粘连,模糊不清。先多西他赛后放疗组的脊髓髓鞘的板层结构部分松解、扭曲;胶质细胞核固缩。先放疗后多西他赛组脊髓损伤髓鞘的板层结构大部分松解、扭曲、断裂;细胞器严重变形;胶质细胞凋亡。各组血管均未见明显改变。结论多西他赛与放疗联用明显加重脊髓损伤,且放疗后加用多西他赛脊髓损伤加重。

Objective To explore the injury of normal spinal cord irradiated by the combination of docetaxel and radiotherapy. Methods In this experiment, 40 Wistar rats were divided groups as following： norrnal, docetaxel, radiation, radiation after docetaxel, docetaxel after radiation. Docetaxel was administrated singlely 5mg/kg. The thoraxs of rats were irradiated with 6MeV electron beam of Varian 2300 C/D line accelerater. The dose of irradiation was 5Gy singlely, and total dose was 40Gy. The size of field was 2cm×4cm. The intervals between docetaxel and radiation in combination group were three days. Rats from each group were sacrificed at 5 months after irradiation. The spinal cord tissues were fixed. The Paraffin sections of spinal cord were examined by microscope, and superthin sections were examined by transmission electron microscope. Results Under microscope, white matterr necrosis partly in groups of radiation and radiation after docetaxel, but white matterr necrosis mostly in docetaxel after docetaxel group. Neuroglia ceil became pycnotic in last two groups. There were not any obvious changes about neuron and blood vessel were observed in all groups. Under electron microscope, spinal cord injured differently in each group. The myelin sheaths of spinal cord became dropsical and dim in radiation group. The myelin sheaths become incompact and twisting partly and neuroglia cell became pycnotic in radiation after docetaxel group. The myelin sheaths become incompact and twisting as well as breaked mostly, and rteuroglia cell became apoptotic in docetaxel after radiation group. There were not any obvious changes about blood vessel were observed in all groups. Conclusion The combination of docetaxel and RT deteriorated the spinal cord injury of rats, especially in docetaxel after radiation group.