Department of Neurosurgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China,
Acta Neurochir (Wien). 2013 Nov;155(11):2063-70; discussion 2069-70. doi: 10.1007/s00701-013-1808-8. Epub 2013 Jul 20.
Akt plays an important role in cell survival, proliferation, apoptosis and other activities. It also has been involved in maintaining smooth muscle cell contraction phenotypes in vitro and in vivo. Recent studies have focused on the inhibition of Akt in acute vasospasm and neuronal apoptosis after subarachnoid hemorrhage (SAH). However, its role in delayed cerebral vasospasm (DCVS) has not been reported.
In this study, using a "two-hemorrhage" rat model of SAH, we examined the expression of p-Akt and the formation of vasospasm in the basilar arteries. To investigate the possible role of Akt in phenotypic switching, we performed immunohistochemical staining to examine expressions of SMα-actin and proliferating cell nuclear antigen (PCNA), markers of smooth muscle phenotypic switching.
We found that the basilar arteries exhibited vasospasm after SAH and that vasospasm became most severe on day 7 after SAH. Elevated protein expression of p-Akt was detected 4 days after SAH induction, peaked on day 7, and recovered on day 21, which was in a parallel time course to the development of DCVS. Moreover, results of immunohistochemical staining revealed enhanced expression of PCNA but gradual reduction in expression of SMα-actin from day 1 to day 7 after SAH; then, the expressions of PCNA and SMα-actin gradually recovered until day 21.
These results support a novel mechanism in which the Akt signaling pathway plays an important role in the proliferation of smooth muscle cells (SMCs) rather than inducing phenotype switching in basilar arteries, which promotes the development of DCVS after SAH.
Akt 在细胞存活、增殖、凋亡等活动中发挥重要作用。它还参与维持平滑肌细胞在体外和体内的收缩表型。最近的研究集中在抑制 Akt 对蛛网膜下腔出血 (SAH) 后急性血管痉挛和神经元细胞凋亡的作用。然而，其在迟发性脑血管痉挛 (DCVS) 中的作用尚未报道。
本研究采用“二次出血”大鼠模型 SAH，检测基底动脉中 p-Akt 的表达和血管痉挛的形成。为了研究 Akt 在表型转换中的可能作用，我们进行了免疫组织化学染色，以检测平滑肌表型转换标志物 SMα-actin 和增殖细胞核抗原 (PCNA) 的表达。
我们发现 SAH 后基底动脉发生血管痉挛，SAH 后第 7 天血管痉挛最严重。SAH 诱导后第 4 天检测到 p-Akt 蛋白表达升高，第 7 天达到高峰，第 21 天恢复，与 DCVS 的发展呈平行时间过程。此外，免疫组织化学染色结果显示，PCNA 的表达从 SAH 后第 1 天到第 7 天逐渐增强，而 SMα-actin 的表达逐渐减少；然后，PCNA 和 SMα-actin 的表达逐渐恢复，直到第 21 天。
这些结果支持了一种新的机制，即 Akt 信号通路在促进 SAH 后 DCVS 发展的平滑肌细胞 (SMCs) 增殖中起重要作用，而不是诱导基底动脉的表型转换。
