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硫化氢补充剂可减轻实验性青光眼的视网膜神经节细胞凋亡。

Hydrogen sulfide supplement attenuates the apoptosis of retinal ganglion cells in experimental glaucoma.

机构信息

Department of Ophthalmology, Ruijin Hospital Affiliated Medical School, Shanghai Jiaotong University, 197 Ruijin Er Road, 200025, Shanghai, China.

Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital Affiliated Medical School, Shanghai Jiaotong University, 197 Ruijin Er Road, 200025, Shanghai, China.

出版信息

Exp Eye Res. 2018 Mar;168:33-48. doi: 10.1016/j.exer.2018.01.004. Epub 2018 Jan 8.

Abstract

Glaucoma is a group of neurodegenerative eye diseases characterized by progressive impairment of visual function due to loss of retinal ganglion cells (RGC). As hydrogen sulfide (HS) was reported to play a role in the process of glaucomatous neuropathy and improve RGC survival in experimental glaucoma, the authors aimed to investigate the anti-apoptosis effect of HS supplement in a rat glaucoma model, and further tried to explore the involved factors in the neuroprotection. A chronic ocular hypertension (COH) rat model induced by intracameral injection of cross-linking hydrogel was employed to simulate glaucoma and 288 rats were subjected to experimental procedures in the present study. After 4 weeks of sodium hydrosulfide (NaHS) administration following COH induction, the apoptosis of RGC isolated from experimented rats as well as apoptosis of neurons in ganglion cell layer (GCL), intrinsic apoptotic pathway activity, mitochondrial function, glial activation, NF-κB pathway activity, NADPH oxidase activity, autophagy activity and TNF-α level in retina were evaluated. The results showed that HS supplement effectively attenuated the apoptosis of RGC in experimental glaucoma, and the neuroprotection by HS might correlate with preservation of mitochondrial function, attenuation of oxidative stress, suppression of glial activation, inhibition of inflammatory pathways and downregulation of autophagy. Our study indicated that HS supplement resulted in significant neuroprotection through attenuation of RGC apoptosis which might be linked with multiple factors in experimental glaucoma. The new therapeutic strategy might potentially contribute to benefit glaucoma treatment, which is worth further concerns.

摘要

青光眼是一组神经退行性眼病,其特征是由于视网膜神经节细胞(RGC)的损失导致视觉功能进行性受损。由于硫化氢(HS)被报道在青光眼性神经病的过程中发挥作用,并在实验性青光眼模型中改善 RGC 的存活,作者旨在研究 HS 补充在大鼠青光眼模型中的抗凋亡作用,并进一步探讨神经保护涉及的因素。通过向眼内注射交联水凝胶来诱导慢性眼压升高(COH)大鼠模型来模拟青光眼,本研究共对 288 只大鼠进行了实验程序。在 COH 诱导后给予硫氢化钠(NaHS)4 周后,评估从实验组大鼠中分离的 RGC 凋亡以及神经节细胞层(GCL)中神经元凋亡、内在凋亡途径活性、线粒体功能、神经胶质激活、NF-κB 途径活性、NADPH 氧化酶活性、自噬活性和视网膜中 TNF-α水平。结果表明,HS 补充有效减轻了实验性青光眼 RGC 的凋亡,HS 的神经保护作用可能与线粒体功能的保持、氧化应激的减轻、神经胶质激活的抑制、炎症途径的抑制以及自噬的下调有关。我们的研究表明,HS 补充通过减轻 RGC 凋亡而导致显著的神经保护作用,这可能与实验性青光眼的多种因素有关。这种新的治疗策略可能对青光眼的治疗有益,值得进一步关注。

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