眼科新进展2025，Vol.45Issue(3)：177-182,201,7.DOI:10.13389/j.cnki.rao.2025.0032
TXNIP/Trx-1通路在调控大鼠视网膜缺血-再灌注后小胶质细胞极化中的作用
Mechanisms underlying the role of the TXNIP/Trx-1 pathway in microglial polarization in rat retinas after retinal ischemia reperfusion
摘要
Abstract
Objective To explore the mechanism of the thioredoxin-interacting protein(TXNIP)/thioredoxin-1(Trx-1)pathway in regulating the polarization of retinal microglia in rats after retinal ischemia-reperfusion(RIR)in rats,and to provide new ideas for the prevention and treatment of retinal ischemia reperfusion injury(RIRI).Methods For-ty-two healthy adult male Sprague-Dawley rats were randomly divided into a Sham group,a RIRI group and a TXNIP siRNA group.The right eye of the rats was experimented.For RIRI and TXNIP siRNA groups,RIRI models were established using the anterior chamber high intraocular pressure method.Rats in the TXNIP siRNA group were given the intravitreal injection of TXNIP siRNA 3 d before modeling.Hematoxylin-eosin(HE)staining was used to analyze retinal histopathologic changes of rats in all groups 24 h after modeling.Immunohistochemical staining of brain-specific homeobox/POU domain proteins 3A(Brn-3a)was made to count the number of retinal ganglion cells(RGCs).The dynamical changes in the number of TXNIP+cells 6 h,24 h,72 h and 7 d after modelling were analyzed through immunohistochemical staining in the RIRI group.The retinal microglia polarization and changes in the expression of TXNIP and Trx-1 proteins in each group were de-tected by double immunofluorescence staining and Western blot 24 h after modeling.Results HE staining results showed that 24 h after modelling,the retinal cells were disordered and the inner retinal layer was thickened and swelled in RIRI and TXNIP siRNA groups,compared with those in the Sham group(all P＜0.05).Immunohistochemical staining results of Brn-3a showed that 24 h after modeling,the number of Brn-3a+cells in RIRI and TXNIP siRNA groups significantly decreased,compared with that in the Sham group(both P＜0.05).The number of Brn-3a+cells in the TXNIP siRNA group was signifi-cantly higher than that in the RIRI group(P＜0.05).Immunohistochemical staining results of TXNIP at different time points after modeling showed that the expression of TXNIP+proteins started to increase 6 h after modeling.The TXNIP+protein level reached a peak at 24 h and then decreased gradually.Western blot results revealed that 24 h after modeling,RIRI and TXNIP siRNA groups had significantly higher TXNIP levels and significantly lower Trx-1 levels than the Sham group(all P＜0.05).Compared with those in the RIRI group,the expression of TXNIP proteins was significantly lower and the expression of Trx-1 proteins was significantly higher in the TXNIP siRNA group(both P＜0.05).Double immunofluores-cence staining showed that 24 h after modeling,Iba1+/CD206+cells were significantly more and Iba1+/CD16+cells were significantly less in the TXNIP siRNA group than those in the RIRI group(both P＜0.05).RIRI and TXNIP siRNA groups had significantly more Ibal+/TXNIP+cells and significantly less Iba1+/Trx-1+cells than the Sham group(both P＜0.05).The number of Iba1+/TXNIP+cells was significantly lower and the number of Iba1+/Trx-1+cells was significantly higher in the TXNIP siRNA group than those in the RIRI group(both P＜0.05).Conclusion RIR activates the TXNIP/Trx-1 path-way to induce the activation of retinal microglia and regulate the polarization of microglia,thereby resulting in RIRI in rats.关键词
视网膜缺血-再灌注损伤/小胶质细胞极化/TXNIP/Trx-1通路/大鼠Key words
retinal ischemia reperfusion injury/microglia polarization/TXNIP/Trx-1 pathway/rats分类
临床医学引用本文复制引用
赵玉泽,王艺文,张丽军,付忻澔,肖培伦,王晓莉,刘建亮,赵岩松..TXNIP/Trx-1通路在调控大鼠视网膜缺血-再灌注后小胶质细胞极化中的作用[J].眼科新进展,2025,45(3):177-182,201,7.基金项目
山东省自然科学基金(编号:ZR2021MH351,ZR2020MH074) （编号:ZR2021MH351,ZR2020MH074）
国家自然科学基金(编号:82071888) （编号:82071888）
山东第二医科大学大学生创新创业训练计划项目(编号:X2022460) （编号:X2022460）
山东第二医科大学附属医院(教学医院)科研发展基金项目(编号:2024FYZ007) （教学医院）
