Nishinaka Anri, Fuma Shinichiro, Inoue Yuki, Shimazawa Masamitsu, Hara Hideaki
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
J Pharmacol Sci. 2017 Jun;134(2):86-92. doi: 10.1016/j.jphs.2017.05.003. Epub 2017 May 27.
Kallidinogenase has been used to treat retinal vein occlusion (RVO) in patients, although there are no evidences on the effects of kallidinogenase on the retinal edema and the non-perfused areas in eyes with a RVO. We have established a murine RVO model with retinal edema and non-perfused areas. The purpose of this study was to evaluate the effects of kallidinogenase on the retinal edema and size of the non-perfused areas in the mouse RVO model. We evaluated the thickness of the retinal layers and size of the non-perfused areas, and the blood flow by laser speckle flowgraphy in RVO model. The effects of an intravenous injection of kallidinogenase on the retinal edema and size of the non-perfused areas were determined. In addition, the expressions of phosphorylated protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) were measured by Western blotting. Our results showed that kallidinogenase reduced the degree of retinal edema and size of the non-perfused areas by an increase in the blood flow in RVO model. Kallidinogenase also increased the levels of phosphorylated Akt and eNOS. These findings indicate that kallidinogenase acted through Akt/eNOS-dependent phosphorylation. Thus, kallidinogenase should be considered as a possible therapeutic agent for RVO patients.
激肽释放酶原已被用于治疗患者的视网膜静脉阻塞（RVO），尽管尚无证据表明激肽释放酶原对RVO患者眼睛的视网膜水肿和无灌注区有何影响。我们建立了一个具有视网膜水肿和无灌注区的小鼠RVO模型。本研究的目的是评估激肽释放酶原对小鼠RVO模型中视网膜水肿和无灌注区大小的影响。我们评估了RVO模型中视网膜各层的厚度、无灌注区的大小以及通过激光散斑血流图测量的血流情况。确定了静脉注射激肽释放酶原对视网膜水肿和无灌注区大小的影响。此外，通过蛋白质免疫印迹法检测了磷酸化蛋白激酶B（Akt）和内皮型一氧化氮合酶（eNOS）的表达。我们的结果表明，在RVO模型中，激肽释放酶原通过增加血流减少了视网膜水肿的程度和无灌注区的大小。激肽释放酶原还增加了磷酸化Akt和eNOS的水平。这些发现表明激肽释放酶原通过Akt/eNOS依赖性磷酸化发挥作用。因此，激肽释放酶原应被视为RVO患者可能的治疗药物。
