摘要
目的探讨人工寒潮促发大鼠脑卒中发病前脑血管内皮细胞粘附分子mRNA的变化。方法48只SD大鼠制成双肾双夹肾血管性高血压大鼠模型,分为寒潮和非寒潮两大组,再按血压水平各分为正常血压组、160～199mmHg、200～219mmHg和≥220mmHg等4个亚组,寒潮箱处理3d后取嘴侧2mm脑片进行VCAM-1、ICAM-1、P-选择素的RT-PCR检测;取视交叉平面连续切片,每8张取1张切片作原位杂交检测血管内皮的VCAM-1、ICAM-1、P-选择素的mRNA水平,取视交叉平面剩余切片及其余脑片连续切片,HE染色,了解是否有卒中病灶。发生脑卒中者被剔出卒中前状态的分析。结果1)在正常血压、160～199mmHg及200～219mmHg血压亚组,寒潮组各级脑血管的VCAM-1、ICAM-1、P-选择素与GAPDH的比值及原位杂交阳性信号均比非寒潮组高;2)在≥220mmHg血压亚组,寒潮组各级脑血管的上述指标均比非寒潮组降低;3)在非寒潮组,各级脑血管的上述指标均随血压升高而升高;在寒潮组,各级脑血管的上述指标也随血压升高而升高,然而在血压≥220mmHg时转为降低。结论长期持续的高血压损害了脑血管内皮的调控功能,血压越高调控功能越差。
Objective To study the changes in the mRNA expression of endothelial cellular adhesion molecules in the cerebral blood vessels in rats with prestroke condition caused by simulated cold wave. Methods Two-kidney two-clip renovascular hypertension was induced in 48 male SD rats, which were subsequently randomly assigned into cold wave exposure and non-exposed group （n=24）. Each group was further divided into 4 sub-groups according to their systolic blood pressure, namely the sham-operated group with blood pressure （BP）〈140 mmHg, mild hypertensive group with BP of 160-199 mmHg, moderate hypertensive group with BP of 200-219 mmHg, and severe hypertensive group with BP no less than 220 mmHg. Cold wave exposure was simulated by housing the rats in an artificial climate chamber with 3 cycles of 12 h light at 22 ℃ and 12 h dark at 4 ℃. The non-exposed group was kept at 22 ℃ throughout the experiment. After the exposure, the rats were sacrificed and the tissues of the frontal lobe were slice into 2.0-mm-thick coronal sections for real-time RT-PCR detection of vascular cell adhesion molecule-1 （VCAM-1）, intercellular adhesion molecule-1 （ICAM-1）, and p-selectin mRNA expressions. The 5.0-μm-thick frozen sections from the bregma section underwent in situ hybridization ofVCAM-1, ICAM-1, and p-selectin. The other sections were stained with HE to observe the infarct lesions, and the rats with cerebral infraction were excluded from the statistical analysis. Results In rats with cold wave exposure-induced prestroke condition and BP 〈220 mmHg, VCAM-1, ICAM-1, and p-selectin mRNA expressions all increased compared with those in the non-exposed group. In rats with BP ≥220 mmHg and Cold exposure, the expressions all decreased to some extent compared with those in the non-exposed treatment. In the non-exposed rats, a positive correlation of BP to VCAM-1, ICAM-1, and p-selectin mRNA expressions were noted, and this correlation was also found in cold-wave-exposed rats with BP 〈220 mmHg; VCAM-1, ICAM-1, and p-selectin mRNA expressions decreased dramatically in the exposed rats with BP ≥220 mmHg compared with those in rats with BP 〈220 mmHg. Conclusion Persistent and severe hypertension impairs the modulatory function of the cerebral vascular endothelia, which is a prerequisite for the stroke vulnerability. The modulatory function deteriorates as the BP further increases.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2008年第11期1954-1959,共6页
Journal of Southern Medical University
基金
国家自然科学基金(30471917)
关键词
人工寒潮
高血压
脑卒中
VCAM-1
ICAM-1
P-选择素
artificial cold exposure
hypertension
stroke
vascular cell adhesion molecule-1
intercellular adhesion molecule- 1
P-selectin
