易损性自发性高血压大鼠巨噬细胞耗竭后脑中动脉结构和内皮功能的改善。
Improvement in middle cerebral artery structure and endothelial function in stroke-prone spontaneously hypertensive rats after macrophage depletion.
机构信息
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan, USA.
出版信息
Microcirculation. 2013 Oct;20(7):650-61. doi: 10.1111/micc.12064.
BACKGROUND
Inflammation is involved in the pathogenesis of hypertension. Hypertensive animals have an increased number of perivascular macrophages in cerebral arteries. Macrophages might be involved in remodeling of the cerebral vasculature. We hypothesized that peripheral macrophage depletion would improve MCA structure and function in hypertensive rats.
METHODS
For macrophage depletion, six-week-old stroke-prone spontaneously hypertensive rats (SHRSP) were treated with CLOD, 10 mL/kg every three or four days, i.p., or vehicle (PBS lipo). MCA structure and function were analyzed by pressure and wire myography.
RESULTS
Blood pressure was not affected by CLOD. The number of perivascular CD163-positive cells per microscopic field was reduced in the brain of SHRSP+CLOD. CLOD treatment caused an improvement in endothelium-dependent dilation after intralumenal perfusion of ADP and incubation with Ach. Inhibition of NO production blunted the Ach response, and endothelium-independent dilation was not altered. At an intralumenal pressure of 80 mmHg, MCA from SHRSP+CLOD showed increased lumen diameter, decreased wall thickness, and wall-to-lumen ratio. Cross-sectional area of pial arterioles from SHRSP+CLOD was higher than PBS lipo.
CONCLUSIONS
These results suggest that macrophage depletion attenuates MCA remodeling and improves MCA endothelial function in SHRSP.
背景
炎症参与了高血压的发病机制。高血压动物的脑动脉周围巨噬细胞数量增加。巨噬细胞可能参与了脑血管重塑。我们假设外周巨噬细胞耗竭将改善高血压大鼠的 MCA 结构和功能。
方法
为了进行巨噬细胞耗竭，将易发生中风的自发性高血压大鼠（SHRSP）用 CLOD（每三到四天腹腔注射 10mL/kg）或载体（PBS 脂质体）处理六周。通过压力和电丝描记术分析 MCA 的结构和功能。
结果
CLOD 对血压没有影响。SHRSP+CLOD 大脑中每个显微镜视野的 CD163 阳性细胞数量减少。腔内灌注 ADP 和孵育 Ach 后，CLOD 治疗可改善内皮依赖性扩张。抑制 NO 产生可使 Ach 反应减弱，而内皮非依赖性扩张不受影响。在腔内压力为 80mmHg 时，SHRSP+CLOD 的 MCA 显示出管腔直径增大、壁厚度减小和壁腔比降低。SHRSP+CLOD 的软脑膜小动脉横截面积高于 PBS 脂质体。
结论
这些结果表明，巨噬细胞耗竭可减轻 MCA 重塑并改善 SHRSP 的 MCA 内皮功能。
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