Li Zhen, Chen Xiao-dong, Ni Shao-kai, Li Jian-wen, Lin Mu-sheng
Department of Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Chin J Traumatol. 2004 Feb;7(1):56-61.
To investigate the neointima formation and the expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) in cuff-induced vascular injury in mouse model, and to examine the effect of angiotensin II type 1 receptor (AT1) blocker, olmesartan, on MCP-1 and TNF-alpha expression and consequently vascular remodeling.
Vascular injury was induced by polyethylene cuff-placement around the mouse femoral artery. Some mice were treated with AT1 receptor blocker, olmesartan, at the dose of 3 mg.kg(-1).day(-1) with an osmotic minipump. Neointima formation and the proliferation of vascular smooth muscle cells (VSMCs) were measured by morphometric analysis and bromodeoxyuridine (BrdU) incorporation. MCP-1 and TNF-alpha expression was detected by Western blot and immunohistochemical staining.
We observed neointima formation 14 days after cuff placement as well as VSMCs proliferation in the media and neointima. Cuff placement also induced MCP-1 and TNF-alpha expression in the media and neointima that the VSMCs specifically existed. Treatment of mice with olmesartan at a dose of 3 mg.kg(-1).day(-1), which did not influence systolic blood pressure, significantly decreased neointima formation and the proliferation of VSMCs. Olmesartan also inhibited MCP-1 and TNF-alpha expression in the injured arteries.
Our results demonstrate that blockade of AT1 receptor inhibits MCP-1 and TNF-alpha expression and thereby improves vascular remodeling.
研究小鼠模型中袖带诱导的血管损伤后新生内膜形成以及单核细胞趋化蛋白-1（MCP-1）和肿瘤坏死因子-α（TNF-α）的表达，并检测1型血管紧张素II受体（AT1）阻滞剂奥美沙坦对MCP-1和TNF-α表达以及血管重塑的影响。
通过在小鼠股动脉周围放置聚乙烯袖带诱导血管损伤。部分小鼠用渗透微型泵以3 mg·kg⁻¹·d⁻¹的剂量给予AT1受体阻滞剂奥美沙坦。通过形态计量分析和溴脱氧尿苷（BrdU）掺入法测量新生内膜形成和血管平滑肌细胞（VSMC）增殖。通过蛋白质免疫印迹法和免疫组织化学染色检测MCP-1和TNF-α表达。
我们观察到袖带放置后第14天出现新生内膜形成以及中膜和新生内膜中的VSMC增殖。袖带放置还诱导了VSMC特异性存在的中膜和新生内膜中MCP-1和TNF-α的表达。以3 mg·kg⁻¹·d⁻¹的剂量用奥美沙坦治疗小鼠，该剂量不影响收缩压，显著减少了新生内膜形成和VSMC增殖。奥美沙坦还抑制了损伤动脉中MCP-1和TNF-α的表达。
我们的结果表明，阻断AT1受体可抑制MCP-Ⅰ和TNF-α的表达，从而改善血管重塑。
