大鼠颅脑冷冻伤后脑水肿和神经元凋亡的变化及其治疗探讨
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摘要
目的：本实验采用冷冻伤性脑水肿模型，测定脑组织含水量变化和观察神经元
凋亡变化规律，并且应用川芎嗪治疗冷冻性颅脑损伤，研究凋亡在颅脑损伤病
理过程中的作用和川芎嗪的治疗效果，探讨颅脑损伤的治疗。
方法：大鼠颅骨外用-196℃致冷冻性颅脑损伤。伤后10分钟从尾静脉注入2％
伊文思蓝（2ml/kg）。应用干湿重法分别测定2小时、6小时和12小时大鼠脑
组织含水量，同时应用TUNEL技术原位分别观察2小时和6小时伤侧皮质和海
马神经元凋亡变化。最后应用川芎嗪（80mg/kg）治疗伤后6小时的冷冻性颅脑
损伤，用二甲基亚砜（0.4g/kg）对比其对脑水肿的影响，并单独观察其对凋亡
的影响。
结果：（1）正常组和假手术组脑组织无伊文思蓝蓝染，而冷冻伤各组有不同程
度的蓝染。（2）脑冷冻伤后脑组织含水量与对照组相比明显增加（P均＜0.05），
在12小时内有上升的趋势，但6小时组与12小时组相比无显著差异（P＞O.05）。
（3）脑冷冻伤后伤侧脑组织神经元凋亡与对照组相比明显增多（P均＜0.05），
2小时组凋亡主要位于伤灶皮质周围和伤灶内，而6小时组凋亡主要位于伤灶
皮质周围和海马。（4）川芎嗪和二甲基亚砜治疗组脑含水量与未治疗组相比均
明显降低（P均＜0.01），但二甲基亚砜组较川芎嗪组更明显（P＜0.01）。川芎嗪
治疗组神经元凋亡与未治疗组相比明显减少（P均＜0.01）。
结论：（1）大鼠颅骨外冷冻伤继发脑水肿模型制作成功，早期即出现血管源性
脑水肿。（2）脑冷冻伤后早期即有明显的神经细胞凋亡存在，坏死位于伤灶中
心区，而凋亡主要位于冻伤灶周围和海马，凋亡与坏死并存。（3）川芎嗪有明
显的抗细胞凋亡和减轻脑水肿的作用。但与二甲基亚砜相比较，其减轻脑水肿
作用较弱。（4）结合临床和本实验结果，颅脑损伤早期除应用脱水剂降颅压治
疗外，应尽早给予抗凋亡药物治疗。作为抗凋亡药物川芎嗪是一个选择，临床
上可以试用，也值得进一步深入的研究。
Objective: Taking the model of cerebral edema caused by frozen injury, this experiment greatly deals with measuring the alternation of brain water content, observing rules of neuronal apoptosis, studying the role of apoptosis in the brain injury, and applying tetramethyl-pyrazine to the treatment of frozen brain injury to have a further study on brain injury.
Methods: Freezing the left parietal bone to -196 to cause a frozen injury, injected % Evans Blue (2ml/kg) into the tail vein 10 minutes later. Took swelling and shrinkage method to measure brain water content of in 2 hours, 6 hours, and 12 hours. Meanwhile, took TUNEL to observe neuronal apopstosis of the cortex and hippocampus in situ in 2 hours and 6 hours. Six hours after the frozen injury was done, tetramethyl-pyrazine was used to treat it. Then compared its effect to water content with the one treated with Dimethyl-Sulfoxide(0. 4g/kg), and observed its effect to apoptosis. Results:
(1): The normal group and the sham-operated controls did not turn blue, but the frozen-injured groups did in different levels. (2): Compared with the controls, Water content of the frozen-injured brain increased obviously (p<0. 05) and had a tendency of increasing within 12 hours. There was no obvious difference between the 6-hour-injured group and 12-hour-injured group( P>0.05) .
(3): Compared with the controls, neuronal apopstosis of injured brain tissue increased (p<0. 05). The apopstosis of 2-hour-injured group mainly appeared in the periphery of cortex surrounding the cold lesion and inside
the cold lesion, while the apopstosis of 6-hour-injured group mainly appeared in the periphery of cortex surrounding the cold lesion and hippocampus.
(4):Compared with the untreated group, the water content of the Tetramethy-pyrazine-treated and dimethyl-sulfoxide-treated groups decreased significantly(p<0.01), and dimethyl sulfoxide shows more ob6vious effect (p<0. 01). Compared with the untreated group, the neuronal apopstosis of dimethyl-sulfoxide-treated group decreased greatly (p<0.01)
Conclus2ion:
(1) : The making of the frozen-injured rat brain edema model succeeded. Vasogenic brain edema appeared at the early time.
(2) : Neuronal Apoptosis appeared early after the frozen injury in the periphery of cortex surrounding the cold lesion, while necrosis simultaneously appeared in the central lesion.
(3) : Tetramethy pyrazine has a significant effect on inhibiting apoptosis and relieving brain edema, but compared with dimethyl sulfoxide, the effect on relieving brain edema is slighter.
(4): According to the clinic experience and this experiment, it can be concluded that except dehydrant pressure-releasing treatment in the early stage of the brain injury, anti-apoptosis medicine treatment should also be taken as early as possible. As an optional anti-apoptosis medicine, tetramethy pyrazine shows good effect. It is worth clinic trying and further studying.
凋亡变化规律，并且应用川芎嗪治疗冷冻性颅脑损伤，研究凋亡在颅脑损伤病
理过程中的作用和川芎嗪的治疗效果，探讨颅脑损伤的治疗。
方法：大鼠颅骨外用-196℃致冷冻性颅脑损伤。伤后10分钟从尾静脉注入2％
伊文思蓝（2ml/kg）。应用干湿重法分别测定2小时、6小时和12小时大鼠脑
组织含水量，同时应用TUNEL技术原位分别观察2小时和6小时伤侧皮质和海
马神经元凋亡变化。最后应用川芎嗪（80mg/kg）治疗伤后6小时的冷冻性颅脑
损伤，用二甲基亚砜（0.4g/kg）对比其对脑水肿的影响，并单独观察其对凋亡
的影响。
结果：（1）正常组和假手术组脑组织无伊文思蓝蓝染，而冷冻伤各组有不同程
度的蓝染。（2）脑冷冻伤后脑组织含水量与对照组相比明显增加（P均＜0.05），
在12小时内有上升的趋势，但6小时组与12小时组相比无显著差异（P＞O.05）。
（3）脑冷冻伤后伤侧脑组织神经元凋亡与对照组相比明显增多（P均＜0.05），
2小时组凋亡主要位于伤灶皮质周围和伤灶内，而6小时组凋亡主要位于伤灶
皮质周围和海马。（4）川芎嗪和二甲基亚砜治疗组脑含水量与未治疗组相比均
明显降低（P均＜0.01），但二甲基亚砜组较川芎嗪组更明显（P＜0.01）。川芎嗪
治疗组神经元凋亡与未治疗组相比明显减少（P均＜0.01）。
结论：（1）大鼠颅骨外冷冻伤继发脑水肿模型制作成功，早期即出现血管源性
脑水肿。（2）脑冷冻伤后早期即有明显的神经细胞凋亡存在，坏死位于伤灶中
心区，而凋亡主要位于冻伤灶周围和海马，凋亡与坏死并存。（3）川芎嗪有明
显的抗细胞凋亡和减轻脑水肿的作用。但与二甲基亚砜相比较，其减轻脑水肿
作用较弱。（4）结合临床和本实验结果，颅脑损伤早期除应用脱水剂降颅压治
疗外，应尽早给予抗凋亡药物治疗。作为抗凋亡药物川芎嗪是一个选择，临床
上可以试用，也值得进一步深入的研究。
Objective: Taking the model of cerebral edema caused by frozen injury, this experiment greatly deals with measuring the alternation of brain water content, observing rules of neuronal apoptosis, studying the role of apoptosis in the brain injury, and applying tetramethyl-pyrazine to the treatment of frozen brain injury to have a further study on brain injury.
Methods: Freezing the left parietal bone to -196 to cause a frozen injury, injected % Evans Blue (2ml/kg) into the tail vein 10 minutes later. Took swelling and shrinkage method to measure brain water content of in 2 hours, 6 hours, and 12 hours. Meanwhile, took TUNEL to observe neuronal apopstosis of the cortex and hippocampus in situ in 2 hours and 6 hours. Six hours after the frozen injury was done, tetramethyl-pyrazine was used to treat it. Then compared its effect to water content with the one treated with Dimethyl-Sulfoxide(0. 4g/kg), and observed its effect to apoptosis. Results:
(1): The normal group and the sham-operated controls did not turn blue, but the frozen-injured groups did in different levels. (2): Compared with the controls, Water content of the frozen-injured brain increased obviously (p<0. 05) and had a tendency of increasing within 12 hours. There was no obvious difference between the 6-hour-injured group and 12-hour-injured group( P>0.05) .
(3): Compared with the controls, neuronal apopstosis of injured brain tissue increased (p<0. 05). The apopstosis of 2-hour-injured group mainly appeared in the periphery of cortex surrounding the cold lesion and inside
the cold lesion, while the apopstosis of 6-hour-injured group mainly appeared in the periphery of cortex surrounding the cold lesion and hippocampus.
(4):Compared with the untreated group, the water content of the Tetramethy-pyrazine-treated and dimethyl-sulfoxide-treated groups decreased significantly(p<0.01), and dimethyl sulfoxide shows more ob6vious effect (p<0. 01). Compared with the untreated group, the neuronal apopstosis of dimethyl-sulfoxide-treated group decreased greatly (p<0.01)
Conclus2ion:
(1) : The making of the frozen-injured rat brain edema model succeeded. Vasogenic brain edema appeared at the early time.
(2) : Neuronal Apoptosis appeared early after the frozen injury in the periphery of cortex surrounding the cold lesion, while necrosis simultaneously appeared in the central lesion.
(3) : Tetramethy pyrazine has a significant effect on inhibiting apoptosis and relieving brain edema, but compared with dimethyl sulfoxide, the effect on relieving brain edema is slighter.
(4): According to the clinic experience and this experiment, it can be concluded that except dehydrant pressure-releasing treatment in the early stage of the brain injury, anti-apoptosis medicine treatment should also be taken as early as possible. As an optional anti-apoptosis medicine, tetramethy pyrazine shows good effect. It is worth clinic trying and further studying.
引文
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