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右美托咪定预处理通过 Toll 样受体 4(TLR4)通路保护视网膜缺血/再灌注损伤并抑制炎症反应。

Dexmedetomidine preconditioning protects against retinal ischemia/reperfusion injury and inhibits inflammation response via toll-like receptor 4 (TLR4) pathway.

机构信息

Anesthesia Department, Huaihe Hospital of Henan University, Kaifeng, Henan Province, PR China.

Anesthesia Department, Huaihe Hospital of Henan University, Kaifeng, Henan Province, PR China.

出版信息

Biomed Pharmacother. 2017 Sep;93:1018-1024. doi: 10.1016/j.biopha.2017.06.050. Epub 2017 Jul 15.

Abstract

BACKGROUND

Retinal ischemia/reperfusion (I/R) injury is one of significant cause of visual dysopia and causes inflammatory response. Dexmedetomidine is widely applied to general/local anaesthesia and has been reported to have extensive anti-inflammatory effect. However, the role of dexmedetomidine in retinal I/R injury is currently unknown. This study investigates the effect of dexmedetomidine preconditioning on retinal I/R injury and explore the related signal mechanism toll-like receptor 4 (TLR4) pathway.

METHODS

Retinal I/R injury model were established with SD rats through periocular injection. Retinal damage was quantified by measuring the thickness of retinal layers, cell counts of retinal ganglion cells (RGCs) and electroretinography (ERG). Apoptosis of retinal cell was detected by TUNEL assay. Protein and mRNA expression of glial fibrillary acidic protein (GFAP) were measured by western blot and real-time quantitate PCR. Bax, Bcl-2 and nuclear factor-κB (NF-κB) in retinas were detected by western blot.

RESULTS

ERG and HE staining showed that dexmedetomidine preconditioning significantly inhibited the histologic damage induced by I/R injury, which expresses apparent concentration dependent. TUNEL demonstrated that apoptosis of retinal cells were reduced by dexmedetomidine. The expression of NF-κB and GFAP were decreased compared I/R blank group.

CONCLUSION

Dexmedetomidine preconditioning suppresses retinal I/R injury and shows effective anti-inflammatory effect by inhibiting TLR4/NF-κB expression.

摘要

背景

视网膜缺血/再灌注(I/R)损伤是视力障碍的重要原因之一,并引起炎症反应。右美托咪定广泛应用于全身/局部麻醉,并已被报道具有广泛的抗炎作用。然而,右美托咪定在视网膜 I/R 损伤中的作用目前尚不清楚。本研究探讨了右美托咪定预处理对视网膜 I/R 损伤的影响,并探讨了相关信号机制 Toll 样受体 4(TLR4)途径。

方法

通过眼周注射建立 SD 大鼠视网膜 I/R 损伤模型。通过测量视网膜层厚度、视网膜神经节细胞(RGC)计数和视网膜电图(ERG)来量化视网膜损伤。通过 TUNEL 测定法检测视网膜细胞凋亡。通过 Western blot 和实时定量 PCR 测量胶质纤维酸性蛋白(GFAP)的蛋白和 mRNA 表达。通过 Western blot 检测视网膜中 Bax、Bcl-2 和核因子-κB(NF-κB)。

结果

ERG 和 HE 染色显示,右美托咪定预处理显著抑制了 I/R 损伤引起的组织学损伤,表现出明显的浓度依赖性。TUNEL 表明,视网膜细胞的凋亡减少了。与 I/R 空白组相比,NF-κB 和 GFAP 的表达降低。

结论

右美托咪定预处理通过抑制 TLR4/NF-κB 表达抑制视网膜 I/R 损伤,表现出有效的抗炎作用。

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