Yu Bu-wei, Xue Qing-sheng, Xia Meng, Wang Ze-jian, Chen Hong-zhuan
Department of Anesthesiology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Zhonghua Yi Xue Za Zhi. 2003 Jul 10;83(13):1176-9.
To investigate the effects of propofol on the three kinds of brain injuries induced by metabolic disorder, neurotoxicity of excitatory amino acid, and oxygen-derived free radicals in rat cerebral cortical and hippocampal slices.
Slices of rat cerebral cortex and hippocampus were made and incubated in normal artificial cerebrospinal fluid (nACSF). Then the rat cerebral cortical and hippocampal slices were divided into 2 categories: propofol group, the slices in which were co-incubated with 5, 50, or 100 micro mol/L propofol for 3 hours, and 3 experimental injury groups. Each experimental injury group was further subdivided into 3 subgroups including the slices of 4 rats. Two hours after normal incubation the slices were co-incubated with 2,3,5-triphenyltetrazolium chloride (TTC). Formazan, the red crystal product were extracted, and ELISA reader was used to read the absorbance at 490 nm (A(490)) so as to quantitatively evaluate the degree of injury.
The values of A(490) of the slices co-incubated with propofol of different concentrations were not significantly different. Compared with those of the control subgroups, the values A490 were significantly decreased in the cerebral cortical and hippocampus slices damaged by OGD, glutamate, and H(2)O(2) injuries (all P < 0.01). The values of A(490) in the subgroups of low and middle concentrations (5 and 50 micro mol/L) of propofol plus OGD or glutamate injury were not significantly different from those of the subgroups of OGD or glutamate injury alone, both in cerebral cortical and hippocampal slices. However, the values of A(490) in the subgroups of high concentration of propofol (100 micro mol/L) plus OGD or glutamate injury was further decreased (P < 0.01). The values of A(490) in the subgroups of low and middle concentrations of propofol plus H(2)O(2) injury were significantly higher than those of the injury subgroup (all P < 0.01), however, however, the values of A490 in the high concentration propofol plus H(2)O(2) injury subgroup were significantly lower than those of the control group (all P < 0.01), even lower than that of the subgroup of H(2)O(2) injury alone.
Propofol has a neuroprotective effect against hydrogen peroxide injury at low and middle concentrations. Propofol of low and middle concentrations does not improve the decrease of the value of A(490). however, propofol of high concentration augments the oxygen-glucose deprivation and glutamate injuries both in the rat cerebral cortical slices and hippocampal slices.
研究丙泊酚对大鼠大脑皮质和海马脑片代谢紊乱、兴奋性氨基酸神经毒性及氧自由基所致三种脑损伤的影响。
制作大鼠大脑皮质和海马脑片,置于正常人工脑脊液(nACSF)中孵育。然后将大鼠大脑皮质和海马脑片分为2组:丙泊酚组,脑片分别与5、50或100 μmol/L丙泊酚共同孵育3小时;3个实验性损伤组。每个实验性损伤组再进一步分为3个亚组,每组4只大鼠的脑片。正常孵育2小时后,脑片与2,3,5 - 三苯基氯化四氮唑(TTC)共同孵育。提取红色结晶产物甲臜,用酶标仪读取490 nm处的吸光度(A(490)),以定量评估损伤程度。
不同浓度丙泊酚共同孵育的脑片A(490)值差异无统计学意义。与对照亚组相比,氧糖剥夺(OGD)、谷氨酸和H₂O₂损伤的大脑皮质和海马脑片A490值显著降低(均P < 0.01)。丙泊酚低、中浓度(5和50 μmol/L)加OGD或谷氨酸损伤亚组的A(490)值,在大脑皮质和海马脑片中与单独OGD或谷氨酸损伤亚组相比差异无统计学意义。然而,丙泊酚高浓度(100 μmol/L)加OGD或谷氨酸损伤亚组的A(490)值进一步降低(P < 0.01)。丙泊酚低、中浓度加H₂O₂损伤亚组的A(490)值显著高于损伤亚组(均P < 0.01),然而,丙泊酚高浓度加H₂O₂损伤亚组的A490值显著低于对照组(均P < 0.01),甚至低于单独H₂O₂损伤亚组。
丙泊酚在低、中浓度时对过氧化氢损伤有神经保护作用。低、中浓度丙泊酚不能改善A(490)值的降低。然而,高浓度丙泊酚在大鼠大脑皮质和海马脑片中均加剧氧糖剥夺和谷氨酸损伤。