大剂量伽玛刀照射后脑组织一氧化氮合酶亚型表达改变及其与急性脑水肿的关系

Changes in expression of brain nitric oxide synthase isoforms and their relationship with acute cerebral edema after Gamma Knife irradiation with a high dose

目的探讨大剂量伽玛刀(γ刀)照射后脑组织一氧化氮合酶(NOS)亚型表达改变及其与急性脑水肿的关系。方法200Gy量γ刀照射正常大鼠脑,采用光镜、电镜、免疫组化及原位杂交技术研究照射后急性脑水肿的发生发展及脑组织NOS亚型表达变化。结果①照射后30min出现急性脑水肿病理改变,照射后2h出现明显血管源性脑水肿,照射后6h出现明显细胞性脑水肿,照射后3d急性脑水肿达高峰。②脑组织NOS亚型表达在照射后30min开始增高,内皮型一氧化氮合酶(eNOS)及诱导型一氧化氮合酶(iNOS)表达分别于照射后2h及6h显著增高,神经元型一氧化氮合酶(nNOS)表达亦增高,但nNOS阳性表达细胞数量较少。3种NOS亚型表达增高持续时间长,伴行于脑水肿的急性发展阶段。结论大剂量γ刀照射后脑组织NOS亚型表达增高与急性脑水肿的发生发展有关。

Objective To study the relation between changes in expression of brain nitric oxide synthase(NOS)isoforms and acute cerebral edema after Gamma Knife irradiation with a high dose.Method The brains of healthy rats were treated with200Gy Gamma Knife irradiation.By light microscopy,electron microscopy,immunohistochemistry and in situ hybridization,we studied the formation and development of acute cerebral edema as well as changes in expression of brain NOS isoforms after irradiation.Results①Acute cerebral edema was observed morphologically30minutes after irradiation,vasogenic cerebral edema and cytotoxic cerebral edema was obvious in2and6hours after irradiation respectively,acute cerebral edema peaked on thind day after irradiation.②The expression of brain NOS isoforms began to increase30minutes after irradiation.The expression of endothelial nitric oxide synthase(eNOS)and inducible nitric oxide synthase(iNOS)markly elevated2and6hours after irradiation respectively.The expression of neuronal nitric oxide synthase(nNOS)also increased,but the number of nNOS-immunoreactive cells was relatively small.These increases persisted for a long period and could be consistently visualized during the acute developmental phase of cerebral edema.Conclusion The increased expression of brain NOS isoforms was related to the formation and development of acute cerebral edema after Gamma Knife irradiation with a high dose