Notch信号通路在大鼠局灶性脑缺血再灌注损伤恢复期的表达变化

目的探讨局灶性脑缺血再灌注损伤恢复期Notch信号通路的表达变化。方法构建SD大鼠大脑中动脉模型(MCAO)。将大鼠分为:对照组(12只),急性期组(24只),恢复期组(24只);急性期组分为3 d和7 d两个亚组,恢复期组分为15d和30d两个亚组。采用RT-PCR和Western blot测定Notch信号分子的mRNA和蛋白的表达变化。结果与对照组大鼠相比,脑缺血再灌注后第3天Delta-like 1、Delta-like 3、Delta-like 4和Jagged 1的mRNA表达水平明显升高(P 0. 05);第30天的表达水平显著低于对照组(P 0. 05)。Notch 1和Notch 2的mRNA表达水平在脑缺血再灌注后第3天显著升高(P 0. 05);第30天,Notch 1(P 0. 05)、Notch 2(P 0. 05)、Notch 3(P 0. 05)和Notch 4(P 0. 01)的mRNA表达水平均显著低于对照组。脑缺血再灌注后第3天Hes-1(P 0. 01)和Hey-1(P 0. 05)的表达水平较对照组均明显升高;第30天,Hes-1和Hey-1的表达水平低于对照组(P 0. 05)。NICD1和NICD2在大脑局灶性缺血后第3天半暗带区的表达水平显著上升(P 0. 05);第30天的表达水平显著下降(P 0. 05)。结论大鼠脑缺血再灌注损伤恢复期可能通过抑制Notch信号通路的表达,起到神经保护作用。

Change in the expression of the Notch signaling pathway in rats with focal cerebral ischemia/reperfusion injury during recovery

Objective To investigate the change in the expression of the Notch signaling pathway in rats with focal cerebral ischemia/reperfusion injury during recovery. Methods Sprague-Dawley rats were used to establish a model of middle cerebral artery occlusion. The rats were divided into control group with 12 rats, acute stage group with 24 rats, and recovery stage group with 24 rats; the rats in the acute stage group were further divided into 3-day and 7-day subgroups, and those in the recovery stage group were divided into 15-day and 30-day subgroups. RT-PCR and Western blot were used to measure the changes in the mRNA and protein expression of Notch signaling molecules. Results Compared with the control group, there were significant increases in the mRNA expression of Delta-like 1, Delta-like 3, Delta-like 4, and Jagged 1 on day 3 after cerebral ischemia/reperfusion (P<0.05) and significantly lower mRNA expression of these molecules on day 30 (P<0.05). On day 3 after cerebral ischemia/reperfusion, there were significant increases in the mRNA expression of Notch 1 and Notch 2; on day 30, compared with the control group, there was significantly lower mRNA expression of Notch 1 (P<0.05), Notch 2 (P<0.05), Notch 3 (P<0.05), and Notch 4 (P<0.01). Compared with the control group, there were significant increases in the expression of Hes-1 (P<0.01) and Hey-1 (P<0.05) on day 3 after cerebral ischemia/reperfusion; on day 30, there was significantly lower expression of Hes-1 and Hey-1 than the control group (P<0.05). There were significant increases in the expression of NICD1 and NICD2 in the penumbra on day 3 after focal cerebral ischemia (P<0.05) and significant reductions on day 30 (P<0.05). Conclusions The inhibition of the Notch signaling pathway during recovery of cerebral ischemia/reperfusion injury may help to protect the nerves.