人工脑脊液冲洗治疗对实验性大鼠脑外伤后低氧诱导因子表达的影响

Effect of focal irrigation with artificial cerebrospinal fluid on the expression of hypoxia-inducible factor after experimental traumatic brain injury

目的探讨人工脑脊液局灶冲洗治疗对实验性大鼠创伤性脑损伤后脑水肿及低氧诱导因子-1α(HIF-1α)表达的影响。方法采用自由落体打击装置制备大鼠创伤性脑损伤模型,分正常对照组、外伤对照组、生理盐水冲洗治疗组及人工脑脊液冲洗治疗组。于伤后30min开始分别以37℃的生理盐水和人工脑脊液进行局灶冲洗治疗维持3h。伤后4h、1、3、5、7d处死留取脑组织标本,采用干湿重法测伤灶脑组织含水量,RT-PCR方法检测HIF-1αmRNA的表达。结果与外伤对照组相比,生理盐水和人工脑脊液治疗组伤灶脑组织水含量明显降低(P<0.05);脑外伤后4h伤灶脑组织中HIF-1αmRNA表达即明显上升,1d达到高峰,持续至3d,5d开始下降,7d降至正常水平;局灶冲洗治疗后,伤后4h、1d、3d和5d各组脑组织HIF-1αmRNA表达均低于外伤对照组相应各时间点(P<0.05);其中以局灶人工脑脊液冲洗治疗效果最佳。结论局灶人工脑脊液冲洗治疗能明显减轻大鼠伤灶脑水肿,有良好的治疗作用;调节HIF-1α的表达是其脑保护作用的机制之一。

Objective To investigate the effect of focal irrigation with artificial cerebrospinal fluid on brain edema and the expression of hypoxia-inducible factor-1α （HIF-1α） following traumatic brain injury （TBI） in rats. Methods Rats were underwent severe lateral controlled cortical impact brain injury. Thirty minutes after TBI, focal irrigation treatment was implement with normal sodium or artificial cerebrospinal fluid, and maintained for 3 hours. Rats were decapitated gh, 1 day, 3 days, 5 days, 7 days after injury. The percentage of water in the injured parietal cerebral cortex, as well as HIF-1αmRNA were measured. Result In TBI rats, significantly elevated brain edema was detected at 4h, 1,3 days after TBI in the injured parietal cerebral cortex, and began to decline at 5 and 7 days. This rise in brain edema was significantly reduced with posttraumatic focal irrigation, especially treated with artificial cerebrospinal fluid. After TBI, the expression of HIF-1 amRNA was significantly increased at 4h, peaked at 1 -3d, and maintained high at 5d compared with Normal group （ P 〈 0.05 ）. The expression of HIF-1αL was significantly reduced at 4h, 1 d, 3d, and 5d after treated with focal irrigation, especially treated with artificial cerebrospinal fluid. Conclusion Focal irrigation with artificial cerebrospinal fluid can reduce traumatic brain edema significantly. To regulate the expression of HIF-1α may be one of its neuropmtective mechanisms.