Department of Ophthalmology, Xiaogan Hospital Affiliated to Wuhan University of Science and Technology, China.
Department of Endocrinology, Xiaogan Hospital Affiliated to Wuhan University of Science and Technology, China.
Adv Clin Exp Med. 2021 Apr;30(4):421-430. doi: 10.17219/acem/130602.
Increased activity of the NF-κB signaling pathway boosts the progression of retinopathy in diabetic rats.
Using a bioinformatics website, we identified a site where miR-874 binds to the NF-κB p65. Therefore, we speculated that miR-874 might improve retinopathy in diabetic rats by inhibiting the NF-κB signaling pathway.
Ten healthy rats were taken as the control group. Sixty streptozotocin (STZ; 60 mg/kg)-induced diabetes model rats were randomly divided into the model group (injection of normal saline), negative control (NC) agomir group (injection of NC mimic), miR-874 agomir group (injection of miR-874 mimic), miR-874 anti-agomir group (injection of miR-874 inhibitor), EVP4593 group (injection of NF-κB signaling pathway antagonist EVP4593), and miR-874 anti-agomir+EVP4593 group (injection of miR-874 inhibitor and EVP4593). All injections were administered into the caudal vein.
miR-874 could target the degradation of p65. Compared with the control group, model rats had reduced miR-874 expression, increased vascular endothelial growth factor (VEGF) and Ang2 protein expression, lowered end-diastolic velocity (EDV) and peak systolic velocity (PSV) of the central retinal artery (CRA) and blood velocity of central retinal vein (CRV) and CRA, heightened plasma viscosity (PV), blood viscosity (BV) and erythrocyte sedimentation rate (ESR) at all shear rates, decreased capillary pericytes (IPCs), increased vascular endothelial cells (VECs), and ascended p65 expression in the retina (all p < 0.05). Thus, it was shown that pathological changes appeared in the retina of diabetic rats. These indices improved in diabetic rats injected with the miR-874 mimic or EVP4593, but deteriorated in those injected with miR-874 inhibitor (all p < 0.05). EVP4593 also could alleviate the aggravation of retinopathy that was caused by miR-874 inhibition in diabetic rats.
miR-874 modulates the NF-κB signaling pathway by targeting the degradation of p65 to further improve the retina of diabetic rats, thus demonstrating the beneficial effect of miR-874 on diabetic retinopathy in rats.
NF-κB 信号通路的活性增加会促进糖尿病大鼠视网膜病变的进展。
我们使用生物信息学网站确定了 miR-874 与 NF-κB p65 结合的位点。因此，我们推测 miR-874 可能通过抑制 NF-κB 信号通路来改善糖尿病大鼠的视网膜病变。
取 10 只健康大鼠作为对照组。60 只链脲佐菌素（STZ；60mg/kg）诱导的糖尿病模型大鼠随机分为模型组（生理盐水注射）、阴性对照（NC）激动剂组（NC 模拟物注射）、miR-874 激动剂组（miR-874 模拟物注射）、miR-874 反义激动剂组（miR-874 抑制剂注射）、EVP4593 组（NF-κB 信号通路拮抗剂 EVP4593 注射）和 miR-874 反义激动剂+EVP4593 组（miR-874 抑制剂和 EVP4593 注射）。所有注射均通过尾静脉进行。
miR-874 可以靶向 p65 的降解。与对照组相比，模型组大鼠 miR-874 表达降低，血管内皮生长因子（VEGF）和 Ang2 蛋白表达增加，视网膜中央动脉（CRA）舒张末期速度（EDV）和收缩期峰值速度（PSV）以及中央视网膜静脉（CRV）和 CRA 的血流速度降低，血浆黏度（PV）、血液黏度（BV）和红细胞沉降率（ESR）在所有剪切率下均升高，毛细血管周细胞（IPCs）减少，血管内皮细胞（VECs）增加，视网膜中 p65 表达升高（均 P<0.05）。因此，糖尿病大鼠视网膜出现了病理变化。miR-874 模拟物或 EVP4593 注射可改善糖尿病大鼠的这些指标，但 miR-874 抑制剂注射则恶化（均 P<0.05）。EVP4593 还可以减轻 miR-874 抑制引起的糖尿病大鼠视网膜病变的加重。
miR-874 通过靶向 p65 的降解来调节 NF-κB 信号通路，从而进一步改善糖尿病大鼠的视网膜，表明 miR-874 对大鼠糖尿病视网膜病变具有有益作用。
