Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
Brain Res. 2012 Oct 30;1482:71-80. doi: 10.1016/j.brainres.2012.08.057. Epub 2012 Sep 7.
Accumulated evidences have established that inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Sulindac is well known as a nonsteroidal anti-inflammatory drug. However, little is known regarding the effect of sulindac in acute cerebral ischemia. Here, we designed this study to investigate the potential protective effects of sulindac in focal cerebral ischemia and the mechanisms underlying in vivo.
Focal cerebral ischemia was induced in male Sprague-Dawley rats by permanent middle cerebral artery occlusion (pMCAO). Sulindac was administrated at dose of 4, 10, or 20mg/kg at 30 min before the operation. Neurological deficit scores, brain water content and infarct volumes were measured at 24h after pMCAO. Immunohistochemistry, western blot and reverse transcription-polymerase chain reaction were used for examining the mediators involved in Wnt/β-catenin signaling pathway, including the positive regulators dishevelled (Dvl) and β-catenin, the negative regulators adenomatous polyposis coli (APC), and P-β-catenin, as well as the downstream targets Bcl-2, Bax and claudin-5.
Compared with Vehicle group, 20mg/kg sulindac reduced neurological deficits, brain water content and infarct volumes. The same dose of sulindac upregulated the expression of Dvl, β-catenin, Bcl2 and claudin-5, and downregulated APC, P-β-catenin and Bax compared with Vehicle group.
These results showed that sulindac had a significant beneficial effect in cerebral ischemia; this effect may be correlated with the activation of the Wnt/β-catenin signaling.
越来越多的证据表明，炎症损伤在脑缺血发病机制中起重要作用，可能成为治疗的靶点。舒林酸是一种众所周知的非甾体抗炎药。然而，关于舒林酸在急性脑缺血中的作用知之甚少。在这里，我们设计了这项研究，以调查舒林酸在局灶性脑缺血中的潜在保护作用及其在体内的机制。
雄性 Sprague-Dawley 大鼠通过永久性大脑中动脉闭塞（pMCAO）诱导局灶性脑缺血。舒林酸在手术前 30 分钟以 4、10 或 20mg/kg 的剂量给药。pMCAO 后 24 小时测量神经功能缺损评分、脑水含量和梗死体积。免疫组织化学、western blot 和逆转录-聚合酶链反应用于检测 Wnt/β-catenin 信号通路中涉及的介质，包括阳性调节剂 Dvl 和 β-catenin、阴性调节剂 APC 和 P-β-catenin 以及下游靶标 Bcl-2、Bax 和 Claudin-5。
与载体组相比，20mg/kg 舒林酸降低了神经功能缺损、脑水含量和梗死体积。相同剂量的舒林酸上调了 Dvl、β-catenin、Bcl2 和 Claudin-5 的表达，下调了 APC、P-β-catenin 和 Bax 与载体组相比。
这些结果表明舒林酸在脑缺血中具有显著的有益作用；这种作用可能与 Wnt/β-catenin 信号的激活有关。
