Hepatocyte growth factor reduces the infarct volume after transient focal cerebral ischemia in rats

Hepatocyte growth factor reduces the infarct volume after transient focal cerebral ischemia in rats
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肝细胞生长因子减少大鼠短暂局灶性脑缺血后的梗塞体积

DOI:
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发表时间:
2001
影响因子:
1.9
通讯作者:
K. Shima
K. Shima
中科院分区:
医学4区
文献类型:
--
作者:
N. Tsuzuki;T. Miyazawa;K. Matsumoto;Toshikazu Nakamura;K. Shima

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肝细胞生长因子(HGF)最初被发现是一种强有力的肝细胞有丝分裂原。据报道,HGF还具有神经营养因子和血管生成因子的功能。本研究探讨了肝细胞生长因子对大鼠短暂性局灶性脑缺血的神经保护作用,其中肝细胞生长因子的抗凋亡和血管生成作用被认为有助于减少梗死体积。脑室内注射重组人肝细胞生长因子可防止右侧大脑中动脉和双侧颈总动脉闭塞120分钟后的神经元死亡。HGF以剂量依赖性方式显著减少梗死体积。在一个单独的系列实验中,我们接下来在组织病理学上研究了HGF对神经元的抗凋亡作用和血管生成作用。在对照组和溶剂组中,在梗死区的内边界观察到大量TUNEL阳性神经元,而在HGF组中,在相应的区域中仅观察到少数TUNEL阳性神经元。HGF组Bcl-2蛋白在缺血后存活神经元中表达明显。肝细胞生长因子组血管板层数量明显高于溶剂组。这些数据表明,肝细胞生长因子似乎有能力防止神经元细胞凋亡的死亡,同时也具有血管生成的影响,在中枢神经系统的影响与短暂的局灶性脑缺血。
Abstract Hepatocyte growth factor (HGF) was originally discovered as a powerful mitogen for hepatocytes. HGF also has been reported to function as a neurotrophic factor as well as an angiogenetic factor. The present study examined the neuroprotective effect of HGF against transient focal cerebral ischemia in rats, in which an anti-apoptotic and an angiogenetic effect of HGF was assumed to contribute to the reduction of the infarct volume. The intraventricular administration of human recombinant HGF prevented neuronal death after 120 min of occlusion in the right middle cerebral artery and the bilateral common carotid arteries. HGF significantly reduced the infarct volume in a dose-dependent manner. In a separate series of experiments, we next histopathologically investigated both the anti-apoptotic effect on neurons and the angiogenetic effect of HGF. A large number of TUNEL positive neurons were observed in the inner boundary of the infarct area in both the control and the vehicle group whereas only a few TUNEL positive neurons were observed in the corresponding area in the HGF group. In the HGF group, Bcl-2 protein was obviously represented in surviving neurons subjected to ischemia. The number of the vascular lamina in HGF group were significantly higher than those in the vehicle group. These data suggest that HGF appears to have an ability to prevent apoptotic neuronal cell death while also possessing an angiogenetic effect in the central nervous system which was affected with transient focal cerebral ischemia.
DOI: 10.1097/00001756-199501000-00040
发表时间: 1995-01-26
期刊: NEUROREPORT
影响因子: 1.7
作者:
CHEN, J;GRAHAM, SH;SIMON, RP
通讯作者: SIMON, RP
DOI: 10.1073/pnas.90.5.1937
发表时间: 1993-03-01
影响因子: 11.1
作者:
GRANT, DS;KLEINMAN, HK;ROSEN, EM
通讯作者: ROSEN, EM
小鼠局灶性脑缺血后 DNA 碎片的原位检测。
DOI: 10.1016/0169-328x(94)00220-9
发表时间: 1995
期刊: Brain research. Molecular brain research
影响因子: --
作者:
Li,Y;Chopp,M;Jiang,N;Zaloga,C
通讯作者: Zaloga,C