Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, China.
Eur Rev Med Pharmacol Sci. 2018 Sep;22(18):5789-5796. doi: 10.26355/eurrev_201809_15904.
To investigate the role of corticotropin releasing hormone (CRH) in diabetic retinopathy of microvascular disease and the potential mechanism.
The diabetic rat model was constructed by a single intraperitoneal injection of streptozotocin (STZ). The expression of CRH in the retina of diabetic rats and wild-type rats was detected by Real-Time Polymerase Chain Reaction (RT-PCR). CRH shRNA or Scr shRNA adenovirus was injected into the eyes of diabetic rats and wild-type rats, respectively. The effect of down-regulated CRH on visual electrophysiology in rats was evaluated. Protein expressions of vascular endothelial growth factor (VEGF) and inflammatory factors that were related to the microvascular lesion after CRH downregulation were detected by Western blot. Furthermore, p38 expression was detected by Western blot to explore whether mitogen-activated protein kinase (MAPK) signaling pathway was involved in the function of retinal endothelial cells regulated by CRH.
The expression of CRH was significantly up-regulated in the retina of diabetic rats. RT-PCR results showed that the mRNA level of CRH in the retina of diabetic rats injected with CRH shRNA was decreased. However, no significant change in CRH level was observed in rats injected with Scr shRNA adenovirus. The down-regulated CRH could improve the diabetes-induced visual impairment and retinal inflammatory response. Moreover, the down-regulated CRH led to a decreased phosphorylation level of p38.
CRH improves the diabetic retinopathy of microvascular disease via the p38-MAPK pathway, which is expected to be a new target for the treatment of diabetic microangiopathy.
探讨促肾上腺皮质激素释放激素（CRH）在糖尿病微血管病变性视网膜病变中的作用及潜在机制。
通过单次腹腔注射链脲佐菌素（STZ）构建糖尿病大鼠模型。采用实时聚合酶链反应（RT-PCR）检测糖尿病大鼠和野生型大鼠视网膜中 CRH 的表达。分别向糖尿病大鼠和野生型大鼠眼内注射 CRH shRNA 或 Scr shRNA 腺病毒，评估下调 CRH 对大鼠视觉电生理学的影响。采用 Western blot 检测下调 CRH 后与微血管病变相关的血管内皮生长因子（VEGF）和炎症因子的蛋白表达。进一步通过 Western blot 检测 p38 的表达，探讨促分裂原活化蛋白激酶（MAPK）信号通路是否参与 CRH 调节视网膜内皮细胞功能。
糖尿病大鼠视网膜中 CRH 的表达明显上调。RT-PCR 结果显示，注射 CRH shRNA 的糖尿病大鼠视网膜中 CRH 的 mRNA 水平降低。然而，注射 Scr shRNA 腺病毒的大鼠中 CRH 水平没有明显变化。下调 CRH 可改善糖尿病引起的视力损害和视网膜炎症反应。此外，下调 CRH 导致 p38 的磷酸化水平降低。
CRH 通过 p38-MAPK 通路改善糖尿病微血管病变性视网膜病变，有望成为治疗糖尿病微血管病变的新靶点。
