The Role of Angiotensin II Receptor Subtype in Ocular Injury

血管紧张素II(Ang II)在心血管结构和血流动力学的调节中起着重要作用。血管紧张素Ⅱ受体有两种主要亚型，分别称为1型(AT_1)和2型(AT_2)受体。最近的研究表明，Ang II通过这些受体调节伤口愈合过程。1.结膜下伤口愈合：雄性野生型(WT；C57BL/6J)、AT_1a&GT；Null(AT_&lt；1a&Gt；KO)和AT_2 Null(AT_2KO)小鼠采用结膜下钝性切割法建立伤口愈合模型。结膜下损伤导致胶原沉积。组织学分析显示，伤后14天，AT_2KO小鼠结膜下胶原沉积高于WT小鼠，AT_1a&GT；KO小鼠低于WT小鼠。伤后7d，包括结膜在内的结膜下组织中I型胶原基因表达水平升高。这一增加在AT_2KO小鼠中显著高于AT_1A和GT；KO小鼠，但低于WT小鼠。为了探讨AT1和AT2受体在胶原合成调控中的作用机制，我们检测了TIMP-1的表达。结膜下损伤后12h，大鼠结膜下组织中mRNA表达水平也明显升高。然而，TIMP-1的表达增加在AT_1a&GT；KO小鼠中显著高于AT_2KO小鼠，但低于WT小鼠。角膜上皮伤口愈合：用Exmer Lazar制作WT和AT_lt；1a&GT；KO雄性小鼠角膜上皮伤口愈合模型。与WT小鼠相比，AT&lt；1a&GT；KO小鼠角膜上皮伤口愈合延迟。AT&lt；1a&GT；KO小鼠上皮细胞BrdU指数低于WT小鼠，提示AT1和AT2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.