Reduction of inflammatory response in the mouse brain with adenoviral-mediated transforming growth factor-β1 expression
Reduction of inflammatory response in the mouse brain with adenoviral-mediated transforming growth factor-β1 expression
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DOI：
10.1161/01.str.32.2.544
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发表时间：
2001-02-01
期刊：
影响因子：
8.3
通讯作者：
Yang, GY
中科院分区：
文献类型：
--
作者：
Pang, L;Ye, W;Yang, GY
背景和目的-趋化因子已被证明在白细胞和单核细胞/巨噬细胞浸润缺血区域中发挥重要作用。本研究的目的是确定活性人转化生长因子-β1（ahTGF-β1）的过度表达是否可以下调单核细胞趋化蛋白-1（MCP-1）、巨噬细胞炎症蛋白-1α（MIP-1α）和细胞间粘附分子-1（ICAM-1）的表达并减轻缺血性脑损伤。方法-转化生长因子-β1（TGF-β1）的过度表达是通过腺病毒基因转移实现的。腺病毒转导五天后，小鼠接受 30 分钟的大脑中动脉闭塞，然后进行 1 至 7 天的再灌注。采用酶联免疫吸附试验和免疫组化检测TGF-β1、MCP-1、MIP-1α和ICAM-1。通过甲酚紫染色测量梗死面积和体积。结果-大脑中动脉闭塞后MCP-1和MIP-1α表达增加，双标免疫染色显示MCP-1与神经元和星形胶质细胞共定位。病毒介导的 TGF-β1 过度表达在测量的时间点显着增加，在 7 至 9 天达到峰值。在过表达ahTGF-β1的小鼠中，MCP-1和MIP-1α的表达减少，但ICAM-1没有减少（P
Background and Purpose-Chemokines have been shown to play an important role in leukocyte and monocyte/macrophage infiltration into ischemic regions. The purpose of this study is to identify whether overexprrssion of the active human transforming growth factor-beta1 (ahTGF-beta1) can downregulate expression of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1 alpha), and intercellular adhesion molecule-1 (ICAM-1) and reduce ischemic brain injury.Methods-Overexpression of transforming growth factor-beta1 (TGF-beta1) was achieved through adenoviral gene transfer. Five days after adenoviral transduction, the mouse underwent 30 minutes of middle cerebral artery occlusion followed by 1 to 7 days of reperfusion. TGF-beta1, MCP-1, MIP-1 alpha, and ICAM-1 were detected by enzyme-linked immunosorbent assay and immunohistochemistry. Infarct areas and volumes were measured by cresyl violet staining.Results-MCP-1 and MIP-1 alpha expression is increased after middle cerebral artery occlusion, and double-labeled immunostaining revealed that MCP-1 is colocalized with neurons and astrocytes. Viral-mediated TGF-beta1 overexpression was significantly greater at measured time points, with a peak at 7 to 9 days. The expression of MCP-1 and MIP-1 alpha, but not ICAM-1, was reduced in the mice overexpressing ahTGF-beta1 (P