控制性低血压对大鼠脑组织HIE-1的影响

Effect of Sustained Low Blood Pressure on HIF-1 in Rat Brain

【目的】通过控制性降压技术观察持续低血压对大鼠脑中缺氧诱导因子一1的表达影响。【方法144只大鼠随机分为：A组（手术对照组），B1组（降压至MAP50mmHg维持0．5h组），B2组（降压至MAP50mmHg维持1h组），B3组（降压至MAP50mmHg维持2h组），C1组（降压至MAP30mmHg维持0．5h组），C2组（降压至MAP30mmHg维持1h组），C3组（降压至MAP30mmHg维持2h组），C1组为8只，其余每组均为6只大鼠，用硝普钠复合艾司络尔诱导控制性低血压。记录降压期间大鼠生命体征、并行血气分析，降压后观察24小时；观察大鼠降压后神经行为功能变化，生存率，脑海马区形态学变化并测定脑组织缺氧诱导因子-1（HIF-1）的表达。【结果】①A、B1、B2、B3组大鼠在术后一天生存率为100％，神经行为功能未见差异。C1组生存率为67％，C2组的生存率均为38％，C3组因实验中死亡率太高（100％）无法完成，故舍去。C1、C2组术后，神经行为功能有差异。②A、B1、B2、B3组脑海马区形态学正常，c1、c2组均见不同程度的组织结构稀疏，细胞水肿、核固缩的现象。③HIF-1的表达B2、B3组与A组比较无统计学意义（P〉0．05），而A组、C1组和C2组各组之间有统计学意义（P〈0．05）。【结论】大鼠脑组织HIF-1表达明显增加与其组织细胞损害加重相关，也可能与其能诱导细胞凋亡有关。HIF-1活性可能是急性缺氧后组织细胞损伤的重要标志物。

[Objective] To explore the effect of sustained low blood pressure by controlled hypotension on the expression of hypoxia-induced factor-1 （HIF-1） in rat brain. [Methods] Forty four SD rats were randomly divided into 7 groups i.e. group A（operation control）, group B1 （MAP 50 mmHg controlled for 30 minutes）, group B2 （MAP 50mmHg controlled for 60 minutes）, group B3 （MAP 50 mmHg controlled for 120 minutes）, group C1 （MAP 30 mmHg controlled for 30 minutes）, group C2 （MAP 30 mmHg controlled for 60 minutes） and group C3 （MAP 30mmHg controlled for 120 minutes）. Except group C1 had 8 SD rats, other 6 groups had 6 SD rats. The combination of sodium nitroprusside （SNP） and esmolol was used to induce hypotension. The vital sign of rats was recorded during controlled hypotension and blood gas analysis was done for 24 hours after controlled hypotension. The neurologic and behavioral function, survival rate and morphological change of brain hippocampus in rats after hypotension were observed, and the expression of HIF-1 in brain tissue was measured. [Results]One day after hypotension, the survival rate in group A, B1, B2 and t33 was 100% ,and that in group C1 and C2 was 67% and 38%, respectively. Neurologic behavior and function had no difference. Group C3 could not achieve and was excluded for too high mortality （100 % ） in the experiment. After operation, neurologic behavior and function in group C1 and C2 had differences. The morphology of brain hippocampus in group A, BI, B2 and B3 was normal. However, group C1 and C2 presented the sparse histological structure, cellular edema and karyopyknosis. There was no statistical significance in HIF-1 expression between group B2 and B3 and group A（ P 〉0.05）, but there was statistical significance in HIF-1 expression among group A , C1 and C2 group （ P〈0.05）. [Conclusion]The result shows that the significantly increased expression of HIF1 is correlated with the aggravation of the damage of tissues and cells, which may be concerned that it can induce the cell apoptosis. The activity of HIF-1 may be an important marker of the damage of tissues and cells induced by acute hypoxia.