Research on the Mechanism of Extra-mild Hypothermia(35℃) on neuronal cell death

超低温（35℃）对神经细胞死亡的机制研究

• 批准号: 16590851
• 负责人: KATAYAMA Yasuo
• 金额: $ 2.3万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590851/
• 关键词: Hypothermia; Rat; Focal Ischemia; Apoptosis; Neuronal cell death; Immunocytochemistry; In situ hybridization; Rho-kinase; ERK; JNK

The aim of this study is to determine whether a rho-kinase inhibitor, fasudil, would prevent neuronal cell death and whether a extra-mild hypothermia (35℃) would enhance the neuroprotective effects of the rho-kinase inhibitor, following transient focal ischemia in rats. Sprague-Dawley rats were subjected to MCAo using an intraluminal suture technique (Nito C et al, Brain Res 1008 : 179-185, 2004) for 2hrs. The rats were reperfused for 24hrs and decapitated for infarct and edema analysis. a rho-kinase inhibitor (fasudil)-treated animals received a continuous injection of fasudil (3.0 or 10.0mg/kg) for 1hrs by after the onset of ischemia, while vehicle-treated groups received same dose of vehicle. Edaravone- treated animals received a twice injection of edaravone at the dose of 3.0mg/kg just after the onset of recirculation and 30min after. During ischemia, temporal muscle and rectal temperatures were monitored and maintained at 37℃ in the treated animals. Animals were randomly divided i … More nto the following four groups (each, n=10) : (I) vehicle-treated group (control) ; (II) low dose fasudil-treated group (3.0mg/kg) ; (III) high dose fasudil-treated group (10.0mg/kg) ; (IV) edaravone-treated group (3.0mg/kg x 2). Temporal muscle and rectal temperatures were maintained during ischemia at 37 ± 0.2℃. Low dose fasudil (II) ameliorated the cortical and striatal ischemic damage compared with the control (I) significantly (p<0.05), whereas high dose fasudil (III) did not decreased the cortical and striatal infarct volume significantly compared with those of groups I and II (p<0.05). Furthermore, low dose fasudil (II) also decreased the cortical and striatal edema volume significantly compared with those of control (I). These results suggest that a rho-kinase inhibitor, fasudil, has a strong neuroprotective effect compared with edaravone that has already been applied clinically in Japan, and that this drug may be a new therapeutic neuroprotective agent for the treatment of acute stroke in clinical field. Less

本研究的目的是确定rho激酶抑制剂法舒地尔是否可以预防神经元细胞死亡，以及超温和低温（35℃）是否会增强rho激酶抑制剂在大鼠短暂局灶性缺血后的神经保护作用。使用腔内缝合技术(Nito C等人，Brain Res 1008：179-185，2004)对Sprague-Dawley大鼠进行MCAo 2小时。将大鼠再灌注24小时并断头用于梗塞和水肿分析。 rho激酶抑制剂（fasudil）治疗的动物在缺血发生后接受连续注射fasudil（3.0或10.0mg/kg）1小时，而媒介物治疗组接受相同剂量的媒介物。依达拉奉治疗的动物在再循环开始后和30分钟后接受两次依达拉奉注射，剂量为3.0mg/kg。在缺血期间，监测治疗动物的颞肌和直肠温度并将其维持在37℃。将动物随机分为以下四组（每组，n=10）：（I）载体治疗组（对照组）； (II)低剂量法舒地尔治疗组(3.0mg/kg)； (III)高剂量法舒地尔治疗组(10.0mg/kg)； (IV)依达拉奉治疗组(3.0mg/kg×2)。缺血期间颞肌和直肠温度维持在37±0.2℃。与对照组（I）相比，低剂量法舒地尔（II）显着改善皮质和纹状体缺血损伤（p<0.05），而高剂量法舒地尔（III）与I组和II组相比，没有显着减少皮质和纹状体梗塞体积（p<0.05）。此外，与对照组（I）相比，低剂量法舒地尔（II）也显着减少了皮质和纹状体水肿体积。这些结果表明，与日本已临床应用的依达拉奉相比，Rho激酶抑制剂法舒地尔具有更强的神经保护作用，该药物可能成为临床领域治疗急性脑卒中的新型治疗性神经保护剂。较少的