Ikeda T, Ikenoue T, Xia X Y, Xia Y X
Department of Obstetrics and Gynecology, Miayzaki Medical College, Japan.
Am J Obstet Gynecol. 2000 Feb;182(2):380-6. doi: 10.1016/s0002-9378(00)70228-6.
Hypoxic-ischemic tolerance can be induced in neonatal rats through hyperthermic preconditioning. The purposes of this study were to determine the interval between hyperthermic preconditioning and a subsequent hypoxic-ischemic insult that would provide optimal neuroprotection against the insult and to examine the relationship between tolerance induction and heat shock protein expression.
On postnatal day 7 Wistar rat pups were separated into the following 2 groups: a heated group (those exposed to 15 minutes of hyperthermic pretreatment at a brain temperature of 41.5 degrees C-42.0 degrees C) and an unheated control group. At 6, 12, 24, 48, and 72 hours after the hyperthermic stress, rats from both groups were exposed to left carotid artery ligation followed by 2 hours of hypoxia (8% oxygen and 92% nitrogen) at 33 degrees C. Twenty animals from each group were used at each time point. All rats were killed at 1 week after hypoxia-ischemia, at which time the brains were processed and neuronal damage in the cortex and hippocampus was assessed histologically. Another set of 7-day-old rats (n = 30) was studied immunohistochemically at 6, 12, 24, 48, and 72 hours after the same hyperthermic treatment. Expression of 72-kd heat shock protein was measured in neuronal, glial, and vascular endothelial cells.
Hyperthermia-induced hypoxic-ischemic tolerance was observed at 6, 12, and 24 hours but not at 48 and 72 hours after hyperthermic preconditioning. Heat shock protein 72 expression in the vascular endothelial cells, rather than in the glial or neuronal cells, was most strongly associated with hypoxic-ischemic tolerance.
These findings suggest that heat shock protein 72 in endothelial cells plays an important role in the acquisition of hypoxic-ischemic tolerance at postnatal day 7, a time when maximal angiogenesis occurs and the blood-brain barrier is still immature.
通过热预处理可诱导新生大鼠产生缺氧缺血耐受性。本研究的目的是确定热预处理与随后的缺氧缺血性损伤之间的间隔时间，该间隔时间能为抵御损伤提供最佳神经保护，并研究耐受性诱导与热休克蛋白表达之间的关系。
出生后第7天的Wistar大鼠幼崽被分为以下2组：加热组（在脑温41.5℃ - 42.0℃下接受15分钟热预处理的大鼠）和未加热对照组。在热应激后6、12、24、48和72小时，两组大鼠均接受左颈动脉结扎，随后在33℃下进行2小时缺氧（8%氧气和92%氮气）。每个时间点每组使用20只动物。所有大鼠在缺氧缺血后1周处死，此时对大脑进行处理，并通过组织学评估皮质和海马中的神经元损伤。另一组7日龄大鼠（n = 30）在相同热疗后6、12、24、48和72小时进行免疫组织化学研究。测量神经元、胶质细胞和血管内皮细胞中72-kd热休克蛋白的表达。
在热预处理后6、12和24小时观察到热诱导的缺氧缺血耐受性，但在48和72小时未观察到。血管内皮细胞而非胶质细胞或神经元细胞中的热休克蛋白72表达与缺氧缺血耐受性最密切相关。
这些发现表明，内皮细胞中的热休克蛋白72在出生后第7天获得缺氧缺血耐受性中起重要作用，此时发生最大程度的血管生成且血脑屏障仍不成熟。
