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本研究利用体外培养大鼠脑微血管内皮细胞(brain microvascular endothelial cells,BMEC)模型,探讨了血管紧张素(Ang)Ⅱ对大鼠脑微血管内皮细胞表达E-selectin和VCAM-1的影响及其机制,并评价了新型AT1受体拮抗剂化合物EXP-2528对其的影响。采用RT-PCR和Western blotting分别检测大鼠脑微血管内皮细胞E-选择素(E-selectin)和血管细粘黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)的mRNA及蛋白的表达。结果显示1×10-7mol.L-1Ang Ⅱ分别孵育4 h和18 h可显著促进BMEC E-selectin及VCAM-1的mRNA及蛋白的表达,应用氯沙坦和新型选择性AT1受体拮抗剂化合物EXP-2528选择性阻断AT1受体对此有明显抑制作用。同时阻断AT1受体和AT2受体也可明显抑制Ang Ⅱ诱导的E-selectin及VCAM-1表达的增加,但是与单独阻断AT1受体相比无明显差异。而选择性阻断AT2受体对Ang Ⅱ诱导的E-selectin及VCAM-1的表达无明显影响。以上实验结果提示,AngⅡ可通过激动AT1受体上调BMEC E-selectin和VCAM-1的表达,参与脑血管疾病的发生发展。
In this study, the effects of angiotensin Ⅱ on E-selectin and VCAM-1 expression in rat brain microvascular endothelial cells were investigated by in vitro cultured rat brain microvascular endothelial cells (BMEC) model and its mechanism , And evaluated the effect of a novel AT1 receptor antagonist compound EXP-2528 on it. The mRNA and protein expression of E-selectin and vascular cell adhesion molecule-1 (VCAM-1) in rat brain microvascular endothelial cells were detected by RT-PCR and Western blotting respectively . The results showed that the mRNA and protein expression of E-selectin and VCAM-1 in BMECs were significantly increased after incubated with 1 × 10-7mol·L-1Ang Ⅱ for 4 and 18 h, respectively. Losartan and a novel selective AT1 receptor antagonist Compound EXP-2528 selectively blocks the AT1 receptor and significantly inhibits this effect. At the same time blocking AT1 receptor and AT2 receptor can also significantly inhibit the Ang Ⅱ-induced E-selectin and VCAM-1 expression increased, but compared with blocking AT1 receptor alone was no significant difference. Selective blocking of AT2 receptor on Ang Ⅱ induced E-selectin and VCAM-1 expression had no significant effect. The above experimental results suggest that AngⅡis involved in the development of cerebrovascular disease by activating the AT1 receptor to upregulate the expression of E-selectin and VCAM-1.