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输注人脐带血细胞可保护大鼠中暑期间免受脑缺血和损伤。

Infusion of human umbilical cord blood cells protect against cerebral ischemia and damage during heatstroke in the rat.

作者信息

Chen S H, Chang F M, Tsai Y C, Huang K F, Lin C L, Lin M T

机构信息

Institute of Clinical Medicine, College of Medicine, National Cheng-Kung University, Tainan, Taiwan.

出版信息

Exp Neurol. 2006 May;199(1):67-76. doi: 10.1016/j.expneurol.2005.11.015. Epub 2006 Jan 6.

Abstract

Intravenously delivered human umbilical cord blood cells (HUCBC) have been previously shown to improve both morphologic and functional recovery of heat-stroked rats. To extend these findings, we examined both the morphologic and functional alterations in the presence of HUCBC or human peripheral mononuclear cells (PBMC) 24 h before initiation of heatstroke. Anesthetized rats, 1 day before the initiation of heatstroke, were divided into three major groups and given the following: (a) serum-free lymphocyte medium (0.3 ml) intravenously; (b) PBMC (5 x 10(6) in 0.3 ml serum-free lymphocyte medium); or (c) HUCBC (5 x 10(6) in 0.3 ml serum-free lymphocyte medium). Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. In vehicle-treated heatstroke rats, their mean arterial pressure, cerebral blood flow, and brain PO(2) were all lower than in normothermic controls after the onset of heatstroke. However, their body temperatures and striatal levels of inducible nitric oxide synthase (iNOS)-dependent NO, ischemia and damage markers (e.g., glycerol, glutamate, and lactate/pyruvate ratio), and neuronal damage in the striatum were all greater. The heatstroke-induced arterial hypotension, cerebral ischemia and hypoxia, and increased levels of iNOS-dependent NO in the striatum were all significantly reduced by pretreatment with HUCBC, but not with PBMC. Moreover, HUCBC were localized by immunohistochemistry and PCR analysis in the injured brain structures and spleen. These findings indicate that HUCBC transplantation, in addition to having therapeutic values, can be a good choice for preventing heatstroke occurrence.

摘要

先前的研究表明,静脉注射人脐带血细胞(HUCBC)可改善中暑大鼠的形态和功能恢复。为了扩展这些发现,我们在中暑开始前24小时检查了HUCBC或人外周血单个核细胞(PBMC)存在时的形态和功能改变。在中暑开始前1天,将麻醉的大鼠分为三大组,并给予以下处理:(a)静脉注射无血清淋巴细胞培养基(0.3 ml);(b)PBMC(5×10⁶个细胞,溶于0.3 ml无血清淋巴细胞培养基中);或(c)HUCBC(5×10⁶个细胞,溶于0.3 ml无血清淋巴细胞培养基中)。另一组大鼠暴露于室温(26℃)下,用作正常体温对照。在接受载体处理的中暑大鼠中,中暑发作后,它们的平均动脉压、脑血流量和脑PO₂均低于正常体温对照。然而,它们的体温、纹状体中诱导型一氧化氮合酶(iNOS)依赖性NO的水平、缺血和损伤标志物(如甘油、谷氨酸和乳酸/丙酮酸比值)以及纹状体中的神经元损伤均更高。通过HUCBC预处理可显著降低中暑诱导的动脉低血压、脑缺血和缺氧以及纹状体中iNOS依赖性NO水平的升高,但PBMC预处理则无此效果。此外,通过免疫组织化学和PCR分析发现HUCBC定位于受损的脑结构和脾脏中。这些发现表明,HUCBC移植除了具有治疗价值外,还可以是预防中暑发生的良好选择。

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