Pifithrin-α reduces cerebral vasospasm by attenuating apoptosis of endothelial cells in a subarachnoid haemorrhage model of rat

作者：Junhao Yan, Xiaomei Yang, Chun-hua CHEN, Qin Hu, Jing Zhao, Xianzhong Shi, Liju Luan, Lei Yang, Li-hua QIN, Changman Zhou · 发表于：Chinese Medical Journal · 年份：2008 · DOI：10.1097/00029330-200803010-00009 · 被引用次数：12 · 研究领域：Intracranial Aneurysms: Treatment and Complications、Traumatic Brain Injury and Neurovascular Disturbances、Intracerebral and Subarachnoid Hemorrhage Research

Background The mechanism of cerebral vasospasm following subarachnoid haemorrhage (SAH) is not understood. Here, we hypothesized that apoptosis of endothelial cells induced by p53 and its target gene em dash p53 upregulated modulator of apoptosis (PUMA) played an important role in development of cerebral vasospasm. We also observed the effects of a p53 inhibitor, pifithrin-α (PFT-α), on reducing the expression of p53 and PUMA, consequently decreasing the apoptosis of endothelial cells and alleviating cerebral vasospasm. Methods Male Sprague-Dawley rats weighing 300–350 g were randomly divided into five groups: a control group (sham surgery), a SAH group, a SAH+dimethyl sulfoxide (DMSO) group, a SAH+PFT-α (0.2 mg/kg) group and a SAH+PFT-α (2.0 mg/kg) group. PFT-α was injected intraperitoneally immediately after SAH. Rats were sacrificed 24 hours after SAH. Western blot and immunohistochemical staining were used to detect the levels of p53, PUMA and caspase-3 protein. In addition, mortality and neurological scores were assessed for each group. Statistical significance was assured by analysis of variance performed in one way ANOVA followed by the Tukey test. The neurological and mortality scores were analyzed by Dunn’s method and Fisher exact test, respectively. Results After SAH, Western blot and immunohistochemical staining showed the levels of p53, PUMA and caspase-3 in the endothelial cells and the numbers of TdT mediated dUTP nick end labelling (TUNEL) positive endothelial ...