| Objective: In the treatment of malignant tumor, radiotherapy is one of the main method. When carrying on radiotherapy for the malignant tumor including head/neck, chest(lung and esophagus), vertebral column and spinal cord, usually spinal cord has been irradiated inevitably, and even it can give rise to patient radioactivity spinal cord injury. At the present time, the treatment of tumor more and more inclines to integrated treatment, especially chemotherapy (CT) and radiotherapy (RT) has been applied widely. Therefore, when radiotherapy is combined chemotherapy, spinal cord injury deteriorates probably by chemotherapy medication autologous cytotoxicity and radiosensitivity. Up to the present day, there are few research for spinal cord injury's mechanism which give rise to by chemotherapy, radiotherapy respectively, and which give rise to by radiotherapy integrated with chemotherapy. In the field, much mechanism can not unexplained. Especially the spinal cord injury's mechanism of chemotherapy medication itself has been given rise to clinical and fundamental researches paying attention to them. In this experiment, the animal model of research for human spinal cord radioactive injury effect was established through adopting the method of chemotherapy integrated with fractionated irradiation. Then we observed the level of rats spinal cord injury and H-E coloration injury spinal cord tissue morphological change when using radiotherapy, chemotherapy respectively or integrated treatment. we observed spinal cord ultramicro structure change through transmission electron microscope, and observed radiotherapy spinal cord injury pathology change characteristic from morphological aspect. By immunohistochemistry coloration for detected caspase-3, Bax, IL-1βand iNOS masculine cell expression, research above-mentioned biotic factor's expression and meaning after rats radioactive spinal cord injury, and research the factor of apoptosis, inflammatory factor and iNOS on spinal cord injury. Furthermore, we preliminary investigate spinal cord injury which caused through chemotherapy medication. This experiment research provides academic foundation for clinical further increasing healing efficacy of radiotherapy being combined chemotherapy and reducing incidence rate of spinal cord injury.Methods: 50 rats were divided four group as following: normal, CT, RT, combination of CT and RT. CT groups were divided into NVB,GEM, cisplatin + NVB and cisplatin + GEM. Combination groups of CT and RT divided into NVB + radiotherapy, GEM + radiotherapy, cisplatin + NVB + radiotherapy, cisplatin + GEM + radiotherapy. There were totally 10 groups and 5 rats in each group. The dose of GEM and NVB is one-off 30mg/kg and 1.5mg/kg respectively; after 30 minutes, the dose of cisplatin is 5mg/kg. The thoraxs of rats were irradiated with 6MeV electron beam. The dose of single irradiation was 5Gy, and total dose was 40Gy. The field was 2cm×4cm. The interval between agents and RT in combination group was three days. Rats from each group were sacrificed at 20 weeks after irradiation. The spinal cord tissues were fixed by 4% Paraformaldehyde. The Paraffin sections of spinal cord were examined by microscope, and extra thin sections were examined by transmission electron microscope.Results: 1.The spinal cord in experimental groups had various changes when observed by microscope and transmission electron microscope. In CT group, it appeared low-grade changes of partial nerve fiber demyelination; In RT group, it appeared midrange denaturation of nerve fiber extensive demyelination; In RT and combination of CT group, it appeared nerve fiber complete demyelination and vein endodermis necrocytosis, even serious denaturation of spongiocyte hyperplasia. The experiment results accorded with the primary pathological change of human radiation myelopathy. 2.Immunohistochemistry coloration showed that blank control group's caspase-3,Bax,IL-1βand iNOS only existed low level foundation expression or non- expression, combination of CT and RT's masculine response expression of spinal cord tissue distinct more strengthener than CT's and RT's. RT group's masculine expression more strengthener than CT group's.Conclution: 1. observing spinal cord morphological change through light microscope pointed out that all group of CT, RT and combination of CT and RT have emerged spinal cord injury's morphological change. In other words, it showed low-grade change of partial nerve fiber demyelination, midrange denaturation of nerve fiber extensive demyelination, nerve fiber complete demyelination and vein endodermis necrocytosis,even serious denaturation of spongiocyte hyperplasia. 2. We draw the conclusion that combination of CT and RT for spinal cord injury was more severer than RT's, which observed spinal cord injury's ultrastructure through transmission electron microscope. cisplatin+GEM for spinal cord injury was more severer than using GEM alone and appearing the change of neuraxon structure disappear. cisplatin+NVB for spinal cord injury was more severer than using NVB alone and appearing the change of white matter demyelination, denaturation and inflammatory cell soakage. 3. The factor of apoptosis such as bax, caspase- 3, inflammatory factor IL-1βand iNOS all had high-expression, which can prove above-mentioned four biotic factor to participating spinal cord injury possibly. Especially masculine expression of caspase-3, Bax, IL-1βand iNOS in combination of CT and RT was more stronger than CT and RT's, which can prove combination of CT and RT being severe for spinal cord injury. 4. Although cisplatin, GEM, NVB had sensibilization for RT, increased tumor's radiosensitivity, and increased effects of treatment, they can increased adverse reaction of normal tissue,even caused injury. Therefore, when using combination of CT and RT in clinical, we should pay attention to adjustment of RT dose and prophylaxis and treatment of injury.
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