Eye Institute, EENT Hospital, Fudan University, Shanghai, China.
Invest Ophthalmol Vis Sci. 2012 May 17;53(6):3047-53. doi: 10.1167/iovs.11-9154.
We explored the relationship between the renin-angiotensin system (RAS) and aquaporins (AQP1 and AQP4 in Müller glia and astrocytes) in diabetic retinopathy (DR) with and without systemic hypertension.
Diabetes was induced in spontaneously hypertensive rats (SHR) and normotensive control Wistar Kyoto (WKY) rats by intraperitoneal injections of streptozotocin. The diabetic and control non-diabetic rats were assigned randomly to receive no anti-hypertension treatment, or to be treated with the angiotensin II receptor blocker (ARB), valsartan (40 mg/kg/d) or the beta-blocker, metoprolol (50 mg/kg/day). Eight weeks later, retinas were evaluated by immunohistochemistry and Western blot to detect changes in the expression of AQP1, AQP4, and glial fibrillary acidic protein (GFAP).
Hypertension increased expression of glial GFAP and AQP4 (P < 0.01), but not AQP1 (P > 0.05) in diabetic rats. Valsartan and metoprolol decreased GFAP, AQP1, and AQP4 expression in diabetic SHR rats (P < 0.01). Valsartan decreased GFAP and AQP1 expression in diabetic WKY rats (P < 0.01), while metoprolol did not.
Activation of Müller glia and astrocytes was involved in the mechanism by which systemic hypertension affects DR. AQPs and macroglia were linked to changes in the RAS in DR. Changes in aquaporin expression in DR were increased by hypertension. This provides additional support for the early use of an ARB in the treatment of DR, especially in cases with retinal edema.
本研究旨在探讨伴有和不伴有系统性高血压的糖尿病视网膜病变（DR）中，肾素-血管紧张素系统（RAS）与水通道蛋白（AQP1 和 AQP4 在 Müller 胶质细胞和星形胶质细胞中的表达）之间的关系。
通过腹腔注射链脲佐菌素诱导自发性高血压大鼠（SHR）和正常血压对照 Wistar Kyoto（WKY）大鼠发生糖尿病。将糖尿病和非糖尿病对照大鼠随机分为不接受抗高血压治疗组，或接受血管紧张素 II 受体阻滞剂（ARB）缬沙坦（40mg/kg/d）或β受体阻滞剂美托洛尔（50mg/kg/天）治疗组。8 周后，通过免疫组织化学和 Western blot 检测评估视网膜中 AQP1、AQP4 和胶质纤维酸性蛋白（GFAP）表达的变化。
高血压增加了糖尿病大鼠中胶质 GFAP 和 AQP4 的表达（P<0.01），但对 AQP1 的表达无影响（P>0.05）。缬沙坦和美托洛尔降低了糖尿病 SHR 大鼠中 GFAP、AQP1 和 AQP4 的表达（P<0.01）。缬沙坦降低了糖尿病 WKY 大鼠中 GFAP 和 AQP1 的表达（P<0.01），而美托洛尔则没有。
全身性高血压影响 DR 的机制涉及 Müller 胶质细胞和星形胶质细胞的激活。AQP 和巨胶质细胞与 DR 中 RAS 的变化有关。DR 中 aquaporin 表达的变化因高血压而增加。这为在 DR 的早期治疗中早期使用 ARB 提供了额外的支持，尤其是在存在视网膜水肿的情况下。
