RESUMO
Ischemic stroke is an acute brain disease with a high mortality rate. Currently, the only effective method is to restore the blood supply. But the inflammation and oxidative stress induced by this approach can damage the integrity of the endothelial system, which hampers the patient's outcome. d-allose has the biological activity to protect against ischemia-reperfusion injury, however, the underlying mechanism remains unclear. Here, brain microvascular endothelial cells (RBMECs) were used as the study material to establish an IR-injury model. Cell viability of RBMECs was suppressed after hypoxia/reoxygenation (H/R) treatment and significantly increased after d-allose supplementation. RNAseq results showed 180 differentially expressed genes (DEGs) between the therapy group (H/R + Dal) and the model group (H/R), of which 151 DEGs were restored to control levels by d-allose. Enrichment analysis revealed that DEGs were mainly involved in protein processing in endoplasmic reticulum. 6 DEGs in the unfolded protein response (UPR) pathway were verified by qRT-PCR. All of them were significantly down-regulated by d-allose, indicating that endoplasmic reticulum stress (ERS) was relieved. In addition, d-allose significantly inhibited the phosphorylation level of eIF2α, a marker of ERS. The downstream molecules of Phosphorylation of eIF2α, Gadd45a and Chac1, which trigger cycle arrest and apoptosis, respectively, were also significantly inhibited by d-allose. Thus, we conclude that d-allose inhibits the UPR pathway, attenuates eIF2α phosphorylation and ERS, restores the cell cycle, inhibits apoptosis, and thus enhances endothelial cell tolerance to H/R injury.
Assuntos
Células Endoteliais , Traumatismo por Reperfusão , Humanos , Células Endoteliais/metabolismo , Estresse do Retículo Endoplasmático , Traumatismo por Reperfusão/metabolismo , Apoptose , Encéfalo/metabolismo , HipóxiaRESUMO
Doubling of the optic disc is rare in clinic, which appears as true doubling or pseudo-doubling. Bilateral doubling of the optic discs is even more less seen in clinic. Here, we report the case of a 35-year-old woman who presented to the clinic for a physical examination. The patient's best-corrected visual acuity was 0.6 OD with +2.25 DS/3.50 DC×175°, and 0.9 OS with -3.00 DS/0.50 DC×145°. The intraocular pressure of each eye was normal. Fundoscopy examination revealed an enlarged suspected optic disc in both eyes. Visual field examination revealed an additional blind spot in each eye. Optical coherence tomography (OCT) analysis showed a normal macular thickness and profile. B-scan ultrasound revealed a single optic nerve shadow in each eye. Cranial computed tomography (CT) showed only 1 optic foramen and 1 optic nerve in each eye. Although double-blind spots were demonstrated by visual field examination, and pits in both optic disc regions for both eyes were shown by OCT, it was not enough to support the diagnosis of true doubling of the optic disc. Consequently, the diagnosis of bilateral pseudo-doubling of optic discs was made based on the clinical evidence, leading to the consideration of possible causality of other ophthalmic diseases.