Department of Rehabilitation, Central Hospital of Linyi, Linyi 276400, Shandong, China.
Department of Pharmacy, The Third People's Hospital of Linyi, Linyi 276000, Shandong, China.
Int Immunopharmacol. 2021 Mar;92:107339. doi: 10.1016/j.intimp.2020.107339. Epub 2021 Jan 27.
Inflammation and oxidative stress is closely associated with the development of ischemic brain stroke. Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1), a novel identified long non-coding RNA (lncRNA), has been suggested to play an important role in the development of many types of human cancers. However, the functional involvement of OIP5-AS1 in ischemic stroke is still unknown.
Quantitative real-time polymerase chain reaction and /or western blot were conducted to determine the expression profiles of OIP5-AS1, C1q/TNF-related protein 3 (CTRP3) and miR-186-5p in the serum of stroke patients, as well as in the ischemic penumbra of rats with middle cerebral artery occlusion/reperfusion (MCAO/R) injury and microglial cells treated with oxygen glucose deprivation/re-oxygenation (OGD/R). Upon selective regulation of OIP5-AS1 and miR-186-5p, the inflammation and oxidative stress responses in microglia/macrophage as well as neurologic functions in MCAO/R rats were detected. Furthermore, the interactions between OIP5-AS1 and miR-186-5p, miR-186-5p and CTRP3 were investigated by RNA immunoprecipitation (RIP) assay, luciferase report assay and bioinformation anaylsis.
We observed markedly increased infarct volume, neuronal apoptosis, inflammation and oxidative stress responses in the infarcted lesions of MCAO/R rats, in line with down-regulated levels of OIP5-AS1 and CTRP3 while up-regulated miR-186-5p. Functional studies demonstrated that up-regulation of OIP5-AS1 attenuated infarct volume, neuronal apoptosis, microglia/macrophage inflammation and oxidative stress responses induced by MCAO/R or OGD/R. In terms of mechanism, we revealed that OIP5-AS1-miR-186-5p-CTRP3 axis played a vital role in modulating microglia/macrophage activation and neuronal apoptosis.
Up-regulating lncRNA OIP5-AS1 protects neuron injury against MCAO/R induced inflammation and oxidative stress in microglia/macrophage through activating CTRP3 via sponging miR-186-5p.
炎症和氧化应激与缺血性脑卒中的发展密切相关。Opa 相互作用蛋白 5 反义 RNA 1（OIP5-AS1）是一种新发现的长非编码 RNA（lncRNA），已被证明在多种人类癌症的发展中发挥重要作用。然而，OIP5-AS1 在缺血性中风中的功能作用尚不清楚。
通过定量实时聚合酶链反应和/或 Western blot 检测中风患者血清以及大脑中动脉闭塞/再灌注（MCAO/R）损伤大鼠缺血半影区和氧葡萄糖剥夺/再氧合（OGD/R）处理的小胶质细胞中 OIP5-AS1、C1q/TNF 相关蛋白 3（CTRP3）和 miR-186-5p 的表达谱。选择性调节 OIP5-AS1 和 miR-186-5p 后，检测 OGD/R 中小胶质细胞/巨噬细胞的炎症和氧化应激反应以及 MCAO/R 大鼠的神经功能。此外，通过 RNA 免疫沉淀（RIP）测定、荧光素酶报告测定和生物信息分析研究 OIP5-AS1 和 miR-186-5p、miR-186-5p 和 CTRP3 之间的相互作用。
我们观察到 MCAO/R 大鼠梗死病灶的梗死体积、神经元凋亡、炎症和氧化应激反应明显增加，同时 OIP5-AS1 和 CTRP3 水平下调，miR-186-5p 水平上调。功能研究表明，上调 OIP5-AS1 可减轻 MCAO/R 或 OGD/R 诱导的梗死体积、神经元凋亡、小胶质细胞/巨噬细胞炎症和氧化应激反应。就机制而言，我们揭示了 OIP5-AS1-miR-186-5p-CTRP3 轴在调节小胶质细胞/巨噬细胞激活和神经元凋亡方面起着至关重要的作用。
上调 lncRNA OIP5-AS1 通过海绵 miR-186-5p 激活 CTRP3，保护神经元免受 MCAO/R 诱导的小胶质细胞/巨噬细胞炎症和氧化应激引起的损伤。
