Neuroprotective effect of Kampo medicine against brain ischemia and its mode of action

汉方药对脑缺血的神经保护作用及其作用机制

基本信息

批准号：
16590556
负责人：
SHIMADA Yutaka
金额：
$ 2.24万
依托单位：
University of Toyama (2005-2006)Toyama Medical and Pharmaceutical University (2004)
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 2006
项目状态：
已结题

项目摘要

Previously, we have revealed that chotosan (Diao-teng-san), a Kampo formula, is effective on vascular dementia clinically, and the hooks and stems of Uncaria sinensis, a medicinal plant comprising chotosan, has a neuroprotective effect in vitro. For the purpose of clarifying their effects in vivo, we investigated whether the oral administration of chotosan extract (CSE) or Uncaria sinensis extract (USE) reduces delayed neuronal death of pyramidal cells in the hippocampus following ischemia/reperfusion (i/rp) in gerbils. CSE or USE were dissolved in drinking water and provided to the gerbils ad libitum from 7 days prior to i/rp until 7 days after i/rp. It was found that CSE-or USE-treatments significantly reduced pyramidal cell death in the hippocampal CA1 region at 7 days after i/rp. Lipid peroxide (LPO) and nitrite (NO_2^-)/nitrate (NO_3^-) levels of the hippocampus at 48 hr after i/rp in the CSE- or USE-treated groups were significantly lower than those of control. Superoxide anion (O_2^-・) and hydroxyl radical (HO・) scavenging activities in both the hippocampus and cortex without i/rp, and also at 3 hours and 7 days after i/rp, were enhanced by the administration of CSE or USE. Administrations of CSE or USE without i/rp procedure enhanced catalase (CAT) activity but not superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in both the hippocampus and cortex. CSE elevated CAT activity in the hippocampus at 7 days and that in the cortex at 3 hours after i/rp. USE raised CAT activity in both the hippocampus and cortex at 3 hours and 7 days after i/rp. These results suggest that the oral administrations of CSE and USE provide a protective effect against transient ischemia-induced delayed neuronal death by reducing oxidative damage to neurons, and one of the mechanisms may be their enhancing effect on CAT activity in the brain.

此前，我们已经发现，汉方配方“吊藤散”在临床上对血管性痴呆有效，而含有壳聚糖的药用植物中华钩藤的钩和茎在体外具有神经保护作用。为了澄清其在体内的影响，我们研究了口服壳聚糖提取物（CSE）或钩藤提取物（USE）是否会延迟锥体细胞的神经元死亡将CSE或USE溶解在沙鼠缺血/再灌注(i/rp)后的海马中，并从i/rp前7天至i/rp后7天随意提供给沙鼠。在 i/rp 后 7 天，CSE 或 USE 治疗显着减少了海马 CA1 区域的锥体细胞死亡。 CSE或USE治疗组在i/rp后48小时海马的(NO_2^-)/硝酸盐(NO_3^-)水平显着低于对照组。在没有 i/rp 的情况下，以及在 i/rp 后 3 小时和 7 天，海马和皮质中的自由基 (HO·) 清除活性通过给予 CSE 或使用CSE或不使用i/rp程序的使用增强了海马和皮质中的过氧化氢酶（CAT）活性，但不增强超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）活性，7。 i/rp 后 3 小时和皮层中的 CAT 活性均在 3 小时和 7 天后提高了海马和皮层中的 CAT 活性。 i/rp.这些结果表明，口服 CSE 和 USE 通过减少对神经元的氧化损伤，对短暂性缺血引起的延迟性神经元死亡具有保护作用，其机制之一可能是它们对大脑中 CAT 活性的增强作用。。