亚低温对复苏后大鼠脑细胞凋亡相关因子的影响

Effect of Mild Hypothermia on the Apoptosis-related Factors in Rats after Resuscitation

目的研究亚低温对心肺复苏后大鼠神经细胞凋亡及凋亡基因表达的影响。方法 60只健康雄性SD大鼠随机分为常温组(T=37℃±0.5℃)和亚低温组(T=33℃±1.0℃),每组30只;窒息法建立心肺复苏模型,于自主循环恢复后12、24h通过神经功能缺损评分评价神经功能,使用TUNEL染色观察脑细胞凋亡情况,并于自主循环恢复后0、2、6、12、24h采用RT-PCR检测脑组织中凋亡诱导因子(apoptosis-inducing factor,AIF)、caspase-3、Fas基因mRNA表达。结果亚低温组大鼠12及24h神经功能缺损评分明显高于常温组(P<0.05),6、12、24h神经细胞凋亡数量明显少于常温组(P<0.05);与常温组相比,自主循环恢复后各时间点AIF、caspase-3及6、12、24hFas基因mRNA表达显著下调(P<0.05)。结论亚低温可能通过抑制脑组织中AIF、caspase-3、Fas凋亡基因表达,减少神经元凋亡,改善神经功能。

Objective To study the effect of mild hypothermia after resuscitation on rat neuronal apoptosisand its gene expression. Methods Sixty healthy male SD rats were equally randomized into two groups ： normaltemperature group （T = 37 ℃ ±0. 5 ℃） and mild hypothermia group （T = 33℃±1.0℃）. A rat model of asphyxial cardiac arrest and cardiopulmonary resuscitation was established. The neurological functions were assessedusing neurological deficit score （ NDS） 12 and 24 hours after the restoration of spontaneous circulation. Also, theexpressions of the apoptosis-inducing factor （AIF）,caspase-3, and Fas mRNA were detected using reverse transcription-polymerase chain reaction （RT-PCR） at 0, 2, 6, 12, and 24 hours, respectively. Results Comparedwith the normal temperature group, the mild hypothermia group had significantly higher NDS at 12 and 24 hours（P 〈 0. 05 ） and lower number of apoptotic brain cells at 6, 12, and 24 hours （ P 〈 0. 05 ） . The mRNA expressions of AIF and caspase-3 at each time point and Fas at 6, 12,24 hours were significantly reduced after resusci-tation in mild hypothermia group （P 〈0. 05）. Conclusion Therapeutic hypothermia after resuscitation may improve NDS and thus protect brain by inhibiting expressions of apoptotic genes including AIF, caspase-3,and Fas.