Curcuma oil modulates the nitric oxide system response to cerebral ischemia/reperfusion injury
Curcuma oil modulates the nitric oxide system response to cerebral ischemia/reperfusion injury
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DOI：
10.1016/j.niox.2008.04.020
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发表时间：
2008-08-01
影响因子：
3.9
通讯作者：
Ray, Madhur
中科院分区：
文献类型：
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作者：
Dohare, Preeti;Varma, Saurabh;Ray, Madhur
C.oil 在脑中风中的抗氧化活性较早已有报道。我们试图阐明姜黄油（C.oil）对实验性脑缺血的神经保护机制，姜黄油是从姜黄根茎中分离出来的。在大鼠因大脑中动脉闭塞（闭塞 1 小时，回流 24 小时）引起局灶性缺血之前 30 分钟给予 C.oil（250 mg/kg i.p.）。缺血会导致 [Ca2+] 升高，这会引发一系列缺血性损伤，而 C.oil 会减弱这种损伤。回流 24 小时后测量时，C.oil 可减少缺血后脑部中性粒细胞浸润，控制组织 NOx 水平以及一氧化氮、过氧亚硝酸盐和活性氧的神经元水平。 C.oil处理后的双重免疫荧光染色分析和Western免疫印迹分析表明，与未处理的缺血组相比，一氧化氮合酶（NOS）亚型的表达显着降低。缺血与脑切片中 TUNEL（TdT 介导的 dUTP 缺口末端标记）阳性细胞的增加有关，表明 DNA 片段化。如神经元的流式细胞术分析所示，与未处理的缺血组相比，C.oil处理组的凋亡细胞数量显着减少。免疫组织化学和 Western 免疫印迹结果表明，Coil 抑制 Bax 蛋白水平升高，并通过改变线粒体膜电位帮助线粒体易位和 Bcl-2 激活。它还抑制细胞色素 c 等致凋亡分子的胞质释放，抑制 caspase-3 的激活和 p53 的表达，最终抑制细胞凋亡。我们的观察表明，NOS 亚型产生的高水平 NO 是加剧 MCAo 管腔内细丝诱导的神经元损伤的部分原因。 (c) 2008 Elsevier Inc. 保留所有权利。
The antioxidant activity of C.oil in cerebral stroke has been reported earlier. We have attempted here to clarify the mechanisms underlying the neuroprotection against experimental cerebral ischemia by Curcuma oil (C.oil), isolated from the rhizomes of Curcuma longa. C.oil (250 mg/kg i.p.) was given 30 min before focal ischemia in rats caused by occlusion of the middle cerebral artery (1 h of occlusion, 24 h of reflow). Ischemia, leads to elevation in [Ca2+] this sets into motion a cascades of ischemic injury which was attenuated by C.oil. C.oil reduced post-ischemic brain neutrophil infiltration in the ischemic area, controlled tissue NOx levels and the neuronal levels of nitric oxide, peroxynitrite and reactive oxygen species when measured after 24 h of reflow. Double immunofluorescence staining analysis and Western immunoblot analysis with C.oil treatment showed that the expression of nitric oxide synthase (NOS) isoforms were decreased significantly compared to the untreated ischemia group. Ischemia is associated with increased in TUNEL (TdT-mediated dUTP nick-end labeling) positive cells in brain sections indicating DNA fragmentation. The C.oil treated group showed a significant decrease in numbers of apoptotic cells compared to the untreated ischemia group, as seen in the flowcytometric analysis of the neurons. Results of immunohistochemistry and Western immunoblot indicate that Coil suppressed the elevated protein level of Bax, and aided mitochondrial translocation and activation of Bcl-2 by altered mitochondrial membrane potential. It also inhibits the cytosolic release of apoptogenic molecules like cytochrome c, inhibits the activation of caspase-3 and the expression of p53 ultimately inhibiting apoptosis. Our observations suggest that high levels of NO generated by NOS isoforms are partially responsible for exacerbating the neuronal damage induced by MCAo by intraluminal filament. (c) 2008 Elsevier Inc. All rights reserved.