丙泊酚对脑挫裂伤后海马边缘c-fos基因表达的影响
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摘要
目的:急性脑挫裂伤患者在神经外科中非常多见,原发性脑挫裂伤一般不需要手术治疗,但当有继发性损害引起颅内高压甚至脑疝形成时,则有手术之必要。术中病人的管理以及选择具备脑保护作用的麻醉药品非常必要丙泊酚作为临床新型麻醉药品,能够降低脑代谢率,减少脑血流量,降低颅内压对神经元具有保护作用逐渐成为研究的热点。C-fos蛋白是即早基因的一种,是联系细胞生化改变与细胞最终对刺激发生特异性反应的中介物,可将其表达及其表达强度作为判断神经细胞损伤程度的分子生物学标志。C-fos基因的高表达与细胞凋亡程度成正比,因此,术中应用具备脑保护作用的麻醉药物,有效降低c-fos蛋白的表达数量,对术后病人的恢复以及降低死亡率有积极的意义。目前应用丙泊酚对脑挫裂伤后c-fos蛋白表达影响的研究较少,本试验观察丙泊酚对脑挫裂伤后海马组织周围c-fos基因表达的影响,从蛋白水平对脑挫裂伤后c-fos蛋白的表达进行研究。
方法:Wistar大鼠30只,雄性。体重(241.6±10.5)随机分为假手术组(A)、脑挫裂伤后对照组(B)和脑挫裂伤后丙泊酚处理组(C),C组按丙泊酚用量60mg/kg.h匀速泵入。采用大鼠脑挫裂伤模型。脑挫裂伤120min时,断头取脑,取全脑石蜡包埋,切片(片厚5um),应用c—fos基因免疫组织化学方法,低倍显微镜(×10)下观察染色阳性细胞的分布情况,高倍镜(×20)下观察鉴别Fos染色免疫阳性细胞并作阳性细胞数.阳性细胞的密度及灰度值,对脑内c-fos蛋白在海马周围组织的表达水平进行检测。
结果:脑挫裂伤后皮层、海马、及海马边缘区等脑区均有c-fos阳性蛋白表达,海马组织周围表达水平明显增高,其中以脑挫裂伤对照组表达最为显著;假手术组仅有少量阳性蛋白的表达,相关剂量的丙泊酚可显著抑制c-fos蛋白在各脑区的表达,尤以海马周围区最为显著。丙泊酚匀速泵入组可明显减少阳性细胞数量,阳性细胞密度。
结论:脑挫裂伤可明显诱导c-fos基因的表达,丙泊酚的脑保护作用可能与其下调c-fos基因的异常表达有关。
Objective: The acute contusion and laceration of brain patient very to see in the neurosurgery department ,The primary contusion and laceration of brain need not the surgery to treat generally But when has the secondary to harm causes acute intracranial hypertension even brain hernia forms, then has necessity of the surgery,In the technique patient's management as well as the choice have the brain protective function narcotic to be essential . As clinical new narcotic,propofolcan cut the brain metabolism rate, reduces the brain blood stream quantity, reduces the cerebrospinal fluid pressure to have the protective function to the neuron to become the research gradually the hot spot. The C-fos protein is one kind of namely early gene.it is relates the cell biochemistry change and the cell has specificity response intermediary finally to the stimulation, May takes its expression and the expression intensity the judgment nerve cell extent of damage the molecular biology symbol. The C-fos gene's high expression and the apoptosis degree is proportional. Therefore, in the technique applies has the brain protective function anaesthesia medicine, reduces the c-fos protein effectively expression quantity, after the technique patient's restoration as well as cuts the mortality rate to have the positive significance. At present after contusion and laceration of brain c-fos the protein expression influence research are few using the propofol.This test observed that the effect of propofolon on c-fos gene of hippocampus after contusion and laceration of brain in rats. after contusion and laceration of brain the c-fos protein expression conducts the research from the protein level .
Methods:30 adult wistar rats,weight(241.6±10.5)g,were randomly divided into three groups:sham opreation group(A) contusion and laceration of brain contral group(B) after contusion and laceration of brain propofol group(C) which was pace infused propofol (60mg/kg). On contusion and laceration of brain in rats model .After contusion and laceration of brain was 120 minutes,cut brain and take tissue of brain. the whole brain was paraffined—inbeded and sliced.C—fos gene immunohistochemical technique was employed to observe and count on the Fos like immunoreactive (FLI) cell ,density of masccline cells,gray scale value c-fos gene of hippocampus expression was detected by immunohistoche - mistr .result: after contusion and laceration of brain, c-fos gene expression was found in the cortex . hippocampus and edge of hippocampus.expression of edge of hippocampus.was raise up obviously .And contusion and laceration of brain contral group(B)is most obvious.Only have few masccline proteinum in sham opreation group(A) .Propofol of correlate dose can abaissement expression of c-fos proteinum on each encephalic region obviously.and edge of hippocampus is the most predominance.
Result:contusion and laceration of brain, the cerebral cortex, edge of hippocampus t, and brain areas and so on seahorse fringe area have the c-fos masculine protein expression, Periphery edge of hippocampus organization expresses the level obvious mark up, contusion and laceration of brain control group by the brain to express obviously. The sham-operation group only has the few masculine protein expression. The related dosage's propofol may obviously suppress the c-fos protein in various brains area expression, is especially most remarkable by the edge of hippocampus. The propofol uniform speed pump enters the group to be possible to reduce the masculine cell quantity, masculine cell density. obviously
Conclusion: contusion and laceration of brain can induce the expression of c-fos obviously,and the brain protection of propofol that can down regulation the c-fos gene.
方法:Wistar大鼠30只,雄性。体重(241.6±10.5)随机分为假手术组(A)、脑挫裂伤后对照组(B)和脑挫裂伤后丙泊酚处理组(C),C组按丙泊酚用量60mg/kg.h匀速泵入。采用大鼠脑挫裂伤模型。脑挫裂伤120min时,断头取脑,取全脑石蜡包埋,切片(片厚5um),应用c—fos基因免疫组织化学方法,低倍显微镜(×10)下观察染色阳性细胞的分布情况,高倍镜(×20)下观察鉴别Fos染色免疫阳性细胞并作阳性细胞数.阳性细胞的密度及灰度值,对脑内c-fos蛋白在海马周围组织的表达水平进行检测。
结果:脑挫裂伤后皮层、海马、及海马边缘区等脑区均有c-fos阳性蛋白表达,海马组织周围表达水平明显增高,其中以脑挫裂伤对照组表达最为显著;假手术组仅有少量阳性蛋白的表达,相关剂量的丙泊酚可显著抑制c-fos蛋白在各脑区的表达,尤以海马周围区最为显著。丙泊酚匀速泵入组可明显减少阳性细胞数量,阳性细胞密度。
结论:脑挫裂伤可明显诱导c-fos基因的表达,丙泊酚的脑保护作用可能与其下调c-fos基因的异常表达有关。
Objective: The acute contusion and laceration of brain patient very to see in the neurosurgery department ,The primary contusion and laceration of brain need not the surgery to treat generally But when has the secondary to harm causes acute intracranial hypertension even brain hernia forms, then has necessity of the surgery,In the technique patient's management as well as the choice have the brain protective function narcotic to be essential . As clinical new narcotic,propofolcan cut the brain metabolism rate, reduces the brain blood stream quantity, reduces the cerebrospinal fluid pressure to have the protective function to the neuron to become the research gradually the hot spot. The C-fos protein is one kind of namely early gene.it is relates the cell biochemistry change and the cell has specificity response intermediary finally to the stimulation, May takes its expression and the expression intensity the judgment nerve cell extent of damage the molecular biology symbol. The C-fos gene's high expression and the apoptosis degree is proportional. Therefore, in the technique applies has the brain protective function anaesthesia medicine, reduces the c-fos protein effectively expression quantity, after the technique patient's restoration as well as cuts the mortality rate to have the positive significance. At present after contusion and laceration of brain c-fos the protein expression influence research are few using the propofol.This test observed that the effect of propofolon on c-fos gene of hippocampus after contusion and laceration of brain in rats. after contusion and laceration of brain the c-fos protein expression conducts the research from the protein level .
Methods:30 adult wistar rats,weight(241.6±10.5)g,were randomly divided into three groups:sham opreation group(A) contusion and laceration of brain contral group(B) after contusion and laceration of brain propofol group(C) which was pace infused propofol (60mg/kg). On contusion and laceration of brain in rats model .After contusion and laceration of brain was 120 minutes,cut brain and take tissue of brain. the whole brain was paraffined—inbeded and sliced.C—fos gene immunohistochemical technique was employed to observe and count on the Fos like immunoreactive (FLI) cell ,density of masccline cells,gray scale value c-fos gene of hippocampus expression was detected by immunohistoche - mistr .result: after contusion and laceration of brain, c-fos gene expression was found in the cortex . hippocampus and edge of hippocampus.expression of edge of hippocampus.was raise up obviously .And contusion and laceration of brain contral group(B)is most obvious.Only have few masccline proteinum in sham opreation group(A) .Propofol of correlate dose can abaissement expression of c-fos proteinum on each encephalic region obviously.and edge of hippocampus is the most predominance.
Result:contusion and laceration of brain, the cerebral cortex, edge of hippocampus t, and brain areas and so on seahorse fringe area have the c-fos masculine protein expression, Periphery edge of hippocampus organization expresses the level obvious mark up, contusion and laceration of brain control group by the brain to express obviously. The sham-operation group only has the few masculine protein expression. The related dosage's propofol may obviously suppress the c-fos protein in various brains area expression, is especially most remarkable by the edge of hippocampus. The propofol uniform speed pump enters the group to be possible to reduce the masculine cell quantity, masculine cell density. obviously
Conclusion: contusion and laceration of brain can induce the expression of c-fos obviously,and the brain protection of propofol that can down regulation the c-fos gene.
引文
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2 张银中.脑外伤患者早期脑缺氧的监测.国外医学麻醉学与复苏分册,1997.17:15
3 孙大金,杭燕南主编.实用 l 临床麻醉学[M】.3 版.北京:中国医药科技出版社,2001,66-457,70
4 庄心良,曾因明,陈伯銮.现代麻醉学[M】.第 3 版.北京:人民卫生出版社,2003,38,481～484,1111
5 Y,Hendler S,Khon RS,et a1.Propofol hemisuccirmte ~ ects neuroml cells frln oxidative jury.J Neu~ hem,1999,73:2524-2530
6 Daskalopoulos R,Korcok J,FarIlj l ee P,et a1.Pro ol p]fot iQof sodium—hyaro exchange aetivi sustains glut.mate ur e dIlrjoxi—dative Stl'e .Anesth Analg,2001.93:l199·1204
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