Anti-monocyte chemoattractant protein-1 gene therapy protects against focal brain ischemia in hypertensive rats
Anti-monocyte chemoattractant protein-1 gene therapy protects against focal brain ischemia in hypertensive rats
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DOI：
10.1097/00004647-200412000-00005
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发表时间：
2004-12-01
影响因子：
6.3
通讯作者：
Iida, M
中科院分区：
文献类型：
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作者：
Kumai, Y;Ooboshi, H;Iida, M
单核细胞趋化蛋白-1 (MCP-1) 在局灶性脑缺血后在缺血皮质中表达，似乎会加剧缺血损伤。作者在高血压大鼠中诱导局灶性脑缺血 90 分钟后检查了显性失活 MCP-1（称为 7ND）基因转移的影响。将编码突变型 MCP-1（Ad7ND；n = 11）的腺病毒载体或作为对照的大肠杆菌 β-半乳糖苷酶（AdlacZ；n = 17）注射到雄性自发性高血压大鼠的侧脑室中。 AdlacZ (n = 12) 和 Ad7ND (n = 6) 给药早在注射后 6 小时就提供了转基因表达，并且表达在第 1 天进一步增加，随后在第 5 天持续检测。缺血五天后，梗塞体积（75 +/- 13 nm(3) (,) n = 5，平均值 +/- SD）显着减少至对照的 72%（104 +/- 22 mm (3)，n = 5，P < 0.05）通过7ND基因转移。 Ad7ND组梗死区血管中白细胞数(48.3+/-32.9/cm(2))和巨噬细胞/单核细胞浸润(475.2+/-125.5/mm(2))显着少于AdlacZ组(143.8+/-72.1/cm(2)和671.8+/-1/cm(2))。 125.5/mm(2)，P < 0.05，分别）。总之，显性失活 MCP-1 的缺血后基因转移减轻了梗塞体积和炎症细胞的浸润，表明抗 MCP-1 基因治疗的潜在用途。
Monocyte chemoattractant protein-1 (MCP-1) is expressed in the ischemic cortex after focal brain ischemia and appears to exacerbate ischemia damage. The authors examined the effect of gene transfer of dominant negative MCP-1, called 7ND, 90 minutes after induction of focal brain ischemia in hypertensive rats. Adenoviral vectors encoding mutant MCP-1 (Ad7ND; n = 11), or Escherichia coli beta-galactosidase (AdlacZ; n = 17) as control were injected into the lateral ventricle of male spontaneously hypertensive rats. Both AdlacZ (n = 12) and Ad7ND (n = 6) administration provided transgene expression as early as 6 hours after injection and the expression further increased on day 1, followed by a sustained detection on day 5. Five days after ischemia, infarct volume (75 +/- 13 nm(3) (,) n = 5, mean +/- SD) significantly reduced to 72% of control (104 +/- 22 mm (3), n = 5, P < 0.05) by 7ND gene transfer. Numbers of leukocytes in the vessels (48.3 +/- 32.9/cm(2)) and macrophage/monocyte infiltration (475.2 +/- 125.5/mm(2)) of the infarct area in the Ad7ND group were significantly less than those measured in the AdlacZ group (143.8 +/- 72.1/cm(2) and 671.8 +/- 125.5/mm(2), P < 0.05, respectively). In summary, the postischemic gene transfer of dominant negative MCP-1 attenuated the infarct volume and infiltration of inflammatory cells, suggesting potential usefulness of the anti-MCP-1 gene therapy.