局部亚低温对实验性脑出血后脑水肿及脑组织核转录因子-κB表达的影响

The changes of nuclear factor-κB expression in perihematoma region and brain edema of experimental intracerebral hemorrhage rats after local mild to moderate hypothermia

目的观察局部亚低温治疗对大鼠脑出血后脑水肿及血肿周围脑组织核转录因子-κB（NF—κB）表达的影响。方法雄性Wistar大鼠144只分成常温组和亚低温组，每组72只，每组又分成相应的对照组、脑出血6h组、脑出血24h组、脑出血48h组、脑出血72h组和脑出血1周组，共6个亚组，每个亚组12只。采用自体不凝血注人大鼠尾状核制备脑出血模型（常温对照组和亚低温对照组手术方法同其余10个亚组，但不注血）。亚低温各亚组造模成功后采用亚低温治疗4h，且维持脑温在（33．0±0．5）℃；常温组保持体温在37℃，常规饲养。应用干湿重法检测脑水肿程度，同时采用免疫组化和免疫印迹方法检测血肿周围NF-κB的表达强度。结果脑出血后48h，常温组和亚低温组大鼠的脑水肿程度和NF—κB表达均达高峰，其中脑水肿程度差异有统计学意义（P〈0．05）。亚低温组中的脑出血24h组、脑出血48h组、脑出血72h组和脑出血1周组的NF—κB阳性细胞表达水平和免疫印迹的蛋白表达强度显著低于常温组相应亚组，差异有统计学意义（P〈0．05）。结论NF—κB高表达是致脑水肿的关键物质，亚低温治疗能明显抑制血肿周围NF—κB的过度表达及脑水肿。

Objective To investigate the effects of local mild to moderate hypothermia on brain edema and nuclear factor-κB （NF-κB） expression in the perihematoma region of experimental intracerebral hemorrhage rats. Methods A total of 144 Wistar rats were randomly divided into a normothermia group and a mild to moderate hypothermia group. The two groups each comprised control, 6 h intracerebral hemorrhage, 24 h intracerebral hemorrhage, 48 h intracerebral hemorrhage, 72 h intracerebral hemorrhage, and 1 week intracerebral hemorrhage subgroups, with 12 rats in each subgroup. Rat models of intracerebral hemorrhage were established by injection of autologous blood into the rat caudate nucleus. Rats in the mild to moderate hypothcrmia group were subject to local mild to moderate hypothermia for 4 hours immediately after the injection, with the intracerebral temperature maintained at （33. 0 ± 0.5 ）℃ , while those in the normothermia were maintained with a body temperature of 37℃. The changes of brain water content were measured and the expression of NF-κB in perihematoma region of intracerebral hemorrhage was observed with immunohistochemistry and Western blot methods. Results The brain edema and the NF-κB expression peaked at 48 h after intracerebral hemorrhage. There was obvious difference in terms of brain edema between the normothennia group and the mild to moderate hypothcrmia group （ P 〈 0.05 ）. The NF-κB expression reduced significantly in the mild to moderate hypothermia group compared with the normothermia group at the 24th,48th and 72nd hours, as well as 1 week after intracerebral hemorrhage （P 〈 0.05）. Conclusions The severity of brain edema was associated with high expression of NF-κB. Treatment with local mild to moderate hypothermia can significantly inhibit overexpression of NF-κB and relieve brain edema following intracerebral hemorrhage.