亚低温对脑缺血-再灌注损伤后神经生长因子前体凋亡前信号的影响

Effects of mild hypothermia on proNGF apoptosis pro-signal following cerebral ischemia and reperfusion

目的探讨脑缺血一再灌注损伤后神经生长因子前体（proNGF）凋亡前信号各因子的表达变化及亚低温对脑损伤的保护作用。方法随机选择体重（220±10）g雌性SD大鼠，分为正常对照组（A组）、脑缺血一再灌注组（B组）、亚低温组（C组），B、C组又分为3，6，9h亚组，动物死亡或模型不成功者剔除，每亚组8只。TUNEL法检测脑缺血-再灌注后及亚低温处理后脑皮质中凋亡细胞数的变化情况。RT—PCR检测每组各时相点脑皮质中proNGF、神经降压素受体3（Sortilin）及P75的表达及变化情况。结果（1）随时间的延长，B组凋亡细胞数增加（P〈0．05），C组相同时相点凋亡数均少于B组（P〈0．05）。（2）三组中各时相点均有各因子的表达，且随损伤时间的延长，表达逐渐上调（P〈0．05）；（3）C组各时相点脑皮质中各因子含量均低于B组（P〈0．05）。结论（1）亚低温可减少脑缺血一再灌注损伤后的细胞凋亡。（2）proNGF所导致的细胞凋亡参与了脑缺血一再灌注损伤的发生、发展过程。（3）亚低温可能通过降低proNGF凋亡前信号的表达来减轻细胞凋亡的发生，从而抑制脑缺血-再灌注损伤后的继发性脑损伤。

Objective To observe the expressional changes of pro nerve growth factor （pro- NGF） apoptosis pro-signal factors after cerebral ischemia and repeffusion and discuss the protective effect of mild hypothermia on the brain injury. Methods The randomly chosen female SD rats weighing （220 ＋_ lO）g were divided into normal control group （Group A）, cerebral ischemia and repeffusion group （ Group B） and mild hypothermia group （ Group C）. Groups B and C were divided into 3, 6 and 9 hours subgroups （ eight rats per group）. TUNEL methods was used to detect the apoptotic cells in the cortex af- ter cerebral isehemia and repeffusion and treatment with mild hypothermia. The reverse transcription poly- merase chain reaction （RT-PCR） was used to detect the expression changes of proNGF, Sortilin and P75 gene in the cortex. Results （ 1 ） The apoptotie cells were increased with time in the Group B （ P 〈 0.05） and were more than those in the Group C in the same time point （P 〈 0.05 ）. （2） There found ex- pression of all factors at all time points in three groups, which was increased with time （ P 〈 0.05 ）. （ 3 ） The content of every factor at each time point in the Group C was less than that in the Group B （ P 〈 0.05 ）. Conclusions （ 1 ） Mild hypothermia can decrease the apoptosis after ischemia and repeffusion injury. （ 2 ） The cell apoptosis induced by proNGF plays a very important role in the course of cerebral is- chemia and repeffusion injury. （3） Mild hypothermia can decrease the expression of apoptosis pro-signal to alleviate the cell apoptosis and protect the brain from ischemia and repeffusion.