摘要
目的观察不同时程治疗性亚低温对大鼠脑出血（ICH）后脑水肿及对缺氧诱导因子-1α（HIF-1α）、血管内皮生长因子（VEGF）表达的影响，探讨亚低温减轻ICH后脑水肿的可能的机制及方法。方法采用自体股动脉血注入右侧基底节区制作ICH模型，将40只雄性SD大鼠，随机（随机数字法）分为5组（各8只）：假手术组（sham）、常温出血组（NT）、亚低温1h组（MH1）、亚低温2h组（MH2）、亚低温4h组（MH3）。NT组、Sham组体温控制（37．0±0．2）℃；亚低温组ICH后即刻快速降至（33．0±0．5）℃并分别持续1、2、4h。在脑出血后48h，各组分别进行脑含水量、血脑屏障通透性检测，应用Real-timePCR及Westernblot检测HIF-1α、VEGFmRNA及蛋白。结果NT组脑含水量、伊文氏蓝含量、HIF-1α、VEGFmRNA及蛋白表达明显高于sham组（P〈0．01）；MH。组与NT组比，HIF-1α mRNA及蛋白表达减少（P〈0．05）；MH2组、MH3组与NT组比，上述指标均下调；MH2组与MH3组结果差异无统计学意义。结论ICH后早期快速的治疗性亚低温可能在转录水平下调HIF-1α mRNA及蛋白表达，进而抑制VEGFmRNA及蛋白，减轻ICH后脑水肿。低温2h与4h对脑水肿的改善相同。
Objective To investigate the effect of mild therapeutic hypothermia for different lengths of time on cerebral edema and hypoxia-inducible factor 1α （HIF-1α）, vascular endothelial growth factor （VEGF） expressions following intracerebral hemorrhage （ICH） so as to explore possible mechanism for better application of mild hypothermia. Methods ICH models were made in rats by stereotaxically injecting autologous artery blood into right caudate nucleus. Forty male Sprague-Dawley （SD） rats were randomly （random number） divided into 5 groups （ n = 8 each） ： sham-operated （ sham）, normothermic （ NT）, hypothermic-1 hour （ MHl ）, hypothermic-2 hours （ MH2 ） , hypothermic-4 hours （ MH3 ）. Normothermic and sham-operated animals were kept at （ 37.0 ± 0. 2） ℃ of body temperature. Animals in＇ the hypothennic groups received immediately and rapid cooling after ICH and kept at （ 33.0 ± 0. 5 ） ℃ of body temperature for 1, 2 and 4 hours respectively. Rats were sacrificed at 48 hours after cerebral hemorrhage. Then brain water content and BBB permeability were determined. Quantitative real-time PCR and Western blot were used to analyze the expression of HIF-1α and VEGF. Results The content of brain water, Evans blue concentration in brain, and the mRNA expression and protein levels of HIF-1α and VEGF were noticeablyhigher in NT group than those in sham gToup （ P 〈 0. 01 ）. There were statistically significant difference in the expression of HIF-1α mRNA and protein but little difference in other indicators between MH1 group and NT group. Compared with NT group, MH2 group and MH3 group brought about an improvement in BBB permeability and remarkable down-regulation of protein levels and expression of HIF-lc~ and VEGF mRNA, whereas there were no statistically significant difference in expression of indicators between the two groups. Conclusions Mild therapeutic hypothermia induced rapidly and immediately after ICH could limit the development of brain edema in rats by down-regulating expression and protein levels of HIF-1α mRNA, and in turn suppressing the evaluation of VEGF mRNA and protein expression. The brain edema was effectively reduced in animals treated with hypothermia for 2 hours ＇ or 4 hours ＇ duration with little difference in magnitude of reduction in brain edema between these two modalities of hypothermia.
出处
《中华急诊医学杂志》
CAS
CSCD
北大核心
2013年第5期496-500,共5页
Chinese Journal of Emergency Medicine
关键词
脑出血
脑水肿
低温
缺氧诱导因子-1Α
血管内皮生长因子
Cerebral hemorrhage
Cerebral edema
Hypothermia
Hypoxia-inducible factor 1α
Vascular endothelial growth factor
