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人脐带血干细胞玻璃体腔内移植可保护大鼠免受创伤性视神经病变。

Intravitreal transplantation of human umbilical cord blood stem cells protects rats from traumatic optic neuropathy.

机构信息

Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha, China.

出版信息

PLoS One. 2013 Aug 5;8(8):e69938. doi: 10.1371/journal.pone.0069938. Print 2013.

Abstract

OBJECTIVES

To treat traumatic optic neuropathy (TON) with transplantation of human umbilical cord blood stem cells (hUCBSC) and explore how transplanted stem cells participate in the neuron repairing process.

METHODS

A total of 195 Sprague-Dawley rats were randomly assigned to three groups: sham-surgery, optic nerve injury, and stem cell transplant group. Optic nerve injury was established in rats by directly clamping the optic nerve for 30 seconds. hUCBSC was microinjected into the vitreous cavity of injured rats. Optic nerve function was evaluated by flash visual evoked potentials (F-VEP). Apoptosis in retina tissues was detected by TUNEL staining. GRP78 and CHOP gene expression was measured by RT-PCR.

RESULTS

After injury, transplantation of hUCBSC significantly blunted a reduction in optic nerve function indicated by smaller decreases in amplitude and smaller increases in peak latency of F-VEP waveform compared to the injury alone group. Also, significant more in retinal ganglion cell (RGC) count and less in RGC apoptosis were detected after transplantation compared to injured rats. The protective effect correlated with upregulated GRP78 and downregulated CHOP mRNA expression.

CONCLUSION

Intravitreal transplantation of hUCBSCs significantly blunted a reduction in optic nerve function through increasing RGC survival and decreasing retinal cell apoptosis. The protective role of transplantation was associated with upregulation of GRP78 expression and downregulation of CHOP expression in retinal cells.

摘要

目的

用人脐带血干细胞(hUCBSC)移植治疗创伤性视神经病变(TON),并探讨移植的干细胞如何参与神经元修复过程。

方法

将 195 只 Sprague-Dawley 大鼠随机分为 3 组:假手术组、视神经损伤组和干细胞移植组。通过直接夹住视神经 30 秒在大鼠中建立视神经损伤。将 hUCBSC 微注射到受伤大鼠的玻璃体腔中。通过闪光视觉诱发电位(F-VEP)评估视神经功能。通过 TUNEL 染色检测视网膜组织中的细胞凋亡。通过 RT-PCR 测量 GRP78 和 CHOP 基因的表达。

结果

与单独损伤组相比,移植 hUCBSC 后,视神经功能明显减弱,F-VEP 波形的振幅减小,峰潜伏期增加。与损伤大鼠相比,移植后视网膜神经节细胞(RGC)计数明显增加,RGC 凋亡明显减少。保护作用与 GRP78 mRNA 表达上调和 CHOP mRNA 表达下调相关。

结论

玻璃体内移植 hUCBSC 可通过增加 RGC 存活和减少视网膜细胞凋亡,显著减轻视神经功能的降低。移植的保护作用与视网膜细胞中 GRP78 表达上调和 CHOP 表达下调有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/887b/3734232/89182a5b2e11/pone.0069938.g001.jpg

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