The Role of Angiotensin II Receptor Subtype in Ocular Injury

血管紧张素II（Angiotensin II，Ang II）在心血管结构和血流动力学的调节中起重要作用。血管紧张素Ⅱ受体有两种亚型，即1型（AT_1）和2型（AT_2）受体。近年来的研究表明，血管紧张素II通过这些受体调节创伤愈合过程。1.结膜下伤口愈合：采用结膜下钝性分离法建立了雄性野生型（WT ; C57 BL/6 J）、AT_<1a>null（AT_<1a>KO）和AT_2 null（AT_2KO）小鼠的伤口愈合模型。结膜下损伤诱导胶原沉积。损伤后14天，组织学检查显示AT_2KO小鼠结膜下胶原沉积高于WT小鼠，但低于AT_<1a>KO小鼠。伤后7天，包括结膜在内的结膜下组织中1型胶原mRNA的水平增加。这种增加在AT_2KO小鼠中显著更高，但低于AT_<1a>KO小鼠中的WT小鼠。为了研究AT 1和AT 2受体对胶原合成调节的作用机制，我们检测了TIMP-1的表达。结膜下损伤后12小时mRNA水平也升高。然而，TIMP-1表达的增加在AT_ KO小鼠中显著高于<1a>WT小鼠，但低于AT_2KO小鼠.角膜上皮伤口愈合：通过准分子lazar在雄性WT和AT_ KO小鼠中制备角膜上皮伤口愈合模型<1a>。与<1a>WT小鼠相比，AT_ KO小鼠延迟角膜上皮伤口愈合。AT_ KO小鼠眼上皮细胞BrdU指数低于<1a>WT小鼠，提示AT_1和AT_2受体亚型在眼损伤的调节中起重要作用。

Angiotensin II (Ang II) plays an important role in the regulation of cardiovascular structure and hemodynamics. Two major Ang II receptor subtypes, named type 1 (AT_1) and type 2 (AT_2) receptors, have been previously reported. Recent studies suggest that Ang II regulates wound healing process through these receptors. However, the detailed mechanism is not clarified We investigated the role of AT_1 and AT_2 receptor subtypes in ocular injury using wound healing model.1.Subconjunctival wound healing : Wound healing model was developed by subconjuncival blunt dissection in male wild type (WT ; C57BL/6J), AT_<1a> null (AT_<1a>KO) and AT_2 null (AT_2KO) mice. Subconjunctival injury induced collagen deposition. Subconjunctival collagen deposition detected by histological analysis at 14 days after injury was higher in AT_2KO mice than in WT mice, but it was lower than in AT_<1a>KO mice than in WT mice. The level of mRNA for type 1 collagen at 7 days was increased in subconjunctival tissue including conjunctiva after injury. This increase was significantly higher in AT_2KO mice, but it was lower than in AT_<1a>KO mice than in WT mice. To examine the mechanism of action of AT1 and AT2 receptors on collagen synthesis regulation, we assayed the expression of TIMP-1. The level of mRNA was also increased at 12 hours after injury after subconjuntival damage. However, the increase in TIMP-1 expression was significantly higher in AT_<1a>KO mice, but lower than in AT_2KO mice than in WT mice.2. Corneal epithelial wound healing : Corneal epithelial wound healing model was made by eximer lazar in male WT and AT_<1a>KO mice. AT_<1a>KO mice delayed corneal epithelial wound healing compared to WT mice. The BrdU index in epithelial cells was lower in the AT_<1a>KO mice than in the WT mice.These results suggest that AT_1 and AT2 receptor subtypes play an important role in the regulation of ocular injury.