[1]李茜,王红星,傅强,等.木犀草素对视网膜缺血-再灌注损伤(RIRI)大鼠TLR4/Syk/NF-κB信号通路及视网膜的影响[J].眼科新进展,2021,41(4):311-316.[doi:10.13389/j.cnki.rao.2021.0065]
　LI Qian,WANG Hongxing,FU Qiang,et al.Effects of luteolin on TLR4/Syk/NF-κB signaling pathway and retina in rats with retinal ischemia-reperfusion injury[J].Recent Advances in Ophthalmology,2021,41(4):311-316.[doi:10.13389/j.cnki.rao.2021.0065]
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木犀草素对视网膜缺血-再灌注损伤(RIRI)大鼠TLR4/Syk/NF-κB信号通路及视网膜的影响/HTML
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《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
41卷
期数:
2021年4期
页码:
311-316
栏目:
实验研究
出版日期:
2021-04-05

文章信息/Info

Title:
Effects of luteolin on TLR4/Syk/NF-κB signaling pathway and retina in rats with retinal ischemia-reperfusion injury
作者:
李茜; 王红星; 傅强; 任泽钦
100022　北京市，清华大学附属垂杨柳医院眼科（李茜，王红星，傅强）；100000　北京市，北京大学人民医院眼科（任泽钦）
Author(s):
LI Qian1; WANG Hongxing1; FU Qiang1; REN Zeqin2
1.Department of Ophthalmology,Chuiyangliu Hospital Affiliated to Tsinghua University,Beijing 100022，China
2.Department of Ophthalmology,People’s Hospital of Peking University,Beijing 100000，China
关键词:
木犀草素; 视网膜缺血-再灌注损伤; Toll样受体4/脾脏酪氨酸激酶/核因子-κB信号通路; 视网膜损伤; 氧化应激
Keywords:
luteolin;  retinal ischemia-reperfusion injury;  Toll-like receptor 4/spleen tyrosine kinase/nuclear factor-κB signaling pathway;  retinal injury;  oxidative stress
分类号:
R774
DOI:
10.13389/j.cnki.rao.2021.0065
文献标志码:
A
摘要:
目的　探讨木犀草素对视网膜缺血-再灌注损伤(RIRI)大鼠Toll样受体4（TLR4）/脾脏酪氨酸激酶（Syk）/核因子-κB（NF-κB）信号通路及视网膜的影响。方法　40只SD大鼠随机分为对照组、模型组、木犀草素低剂量组（5 mg·kg-1）、木犀草素高剂量组（10 mg·kg-1），每组10只，除对照组外，其余各组大鼠制备RIRI模型，造模成功后分别进行腹腔注射不同试剂处理，每天1次，持续 7 d。各组大鼠给药结束后24 h行光学相干断层扫描（OCT）检查，测量视盘周围视网膜厚度；取各组大鼠视网膜行HE染色观察视网膜组织病理形态、行TUNEL染色观察视网膜组织细胞凋亡情况；行酶联免疫吸附试验（ELISA）测定各组大鼠视网膜中超氧化物歧化酶（SOD）活性及丙二醛（MDA）水平，并检测大鼠视网膜中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）水平；利用Western blot检测各组大鼠视网膜TLR4/Syk/NF-κB信号通路相关蛋白表达水平。结果　与对照组相比，模型组大鼠视网膜出现水肿、空泡变性及凋亡等损伤，视网膜厚度［（156.31±18.76）μm］、视网膜神经节细胞数［（66.25±15.18）个·mm-1］、SOD活性［（50.33±1.98）U·mg-1］均显著降低（均为P<0.05），视网膜细胞凋亡率［（21.36±2.04）%］、视网膜中MDA［（1.82±0.14）μmol·g-1］、TNF-α［（98.42±11.25）g·L-1］、IL-6［（87.34±7.62）g·L-1］含量及TLR4、p-Syk/Syk、p-NF-κB/NF-κB蛋白相对表达水平均显著升高（均为P<0.05）。与模型组相比，木犀草素低剂量组、木犀草素高剂量组大鼠视网膜水肿等损伤程度逐渐减轻，视网膜厚度［（170.62±12.46）μm、（183.54±13.75）μm］、视网膜神经节细胞数［（86.74±16.21）个·mm-1、（105.44±14.23）个·mm-1］、SOD活性［（65.26±2.64）U·mg-1、（73.48±3.13）U·mg-1］均依次增加（均为P<0.05），视网膜细胞凋亡率［（16.75±1.55）%、（9.65±1.23）%］、视网膜中MDA［（1.23±0.12）μmol·g-1、（0.86±0.09）μmol·g-1］、TNF-α［（61.48±8.37）g·L-1、（36.83±8.49）g·L-1］、IL-6［（55.47±6.12）g·L-1、（38.71±3.85）g·L-1］含量及TLR4、p-Syk/Syk、p-NF-κB/NF-κB蛋白相对表达水平均依次降低（均为P<0.05）。结论　木犀草素可抑制RIRI大鼠TLR4/Syk/NF-κB信号激活，减轻视网膜组织氧化应激及炎症损伤，进一步减轻视网膜损伤。
Abstract:
Objective　To investigate the effects of luteolin on Toll-like receptor 4 (TLR4)/spleen tyrosine kinase (Syk)/nuclear factor-κB (NF-κB) signaling pathway and retinal injury in rats with retinal ischemia-reperfusion injury.Methods　SD rats (40) were randomly divided into control group, model group, luteolin low dose (5 mg·kg-1) group and luteolin high dose (10 mg·kg-1) group, with 10 rats in each group. Retinal ischemia-reperfusion rat models were established in model group, luteolin low dose group and luteolin high dose group. After successful modeling, the injection of different agents was carried out once a day for 7 days. Twenty-four hours after administration, optical coherence tomography (OCT) was used to measure the retinal thickness around the optic disc in rats; hematoxylin eosin staining (HE) was used to detect the pathological morphology of rat retina; apoptosis of retinal tissue cells was detected by TUNEL staining; the activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) in retina were measured by enzyme-linked immunosorbent assay (ELISA); the levels of inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected by ELISA; Western blot was used to detect the expression levels of TLR4/Syk/NF-κB signaling pathway related proteins in rat retina of groups.Results　Compared with the control group, the retinal edema, vacuolar degeneration and apoptosis appeared in the model group, and the retinal thickness［(156.31±18.76) μm］, the number of retinal ganglion cells ［(66.25±15.18) cells·mm-1］ and SOD activity ［(50.33±1.98) U·mg-1］ were significantly decreased (all P<0.05), while the apoptosis index of retinal cells ［(21.36±2.04)%］, MDA ［(1.82±0.14) μmol·g-1］, TNF-α ［(98.42±11.25) g·L-1］ and IL-6 levels ［(87.34±7.62) g·L-1］, protein expression levels of TLR4, p-Syk/Syk, p-NF-κB/NF-κB were significantly increased (all P<0.05). Compared with the model group, the degree of retinal edema in luteolin low dose group and luteolin high dose group was gradually reduced, and the retinal thickness ［(170.62±12.46) μm, (183.54±13.75) μm, respectively］, the number of retinal ganglion cells ［(86.74±16.21)cells·mm-1，(105.44±14.23) cells·mm-1, respectively］ and SOD activity ［(65.26±2.64)U·mg-1, (73.48±3.13)U·mg-1, respectively］were increased in turn (all P<0.05), while the apoptosis index of retinal cells［(16.75±1.55)%, (9.65±1.23)%, respectively］, MDA ［(1.23±0.12) μmol·g-1, (0.86±0.09) μmol·g-1, respectively］, TNF-α ［(61.48±8.37)g·L-1, (36.83±8.49)g·L-1, respectively］ and IL-6 levels ［(55.47±6.12)g·L-1, (38.71±3.85)g·L-1, respectively］, protein expression levels of TLR4, p-Syk/Syk, p-NF-κB/NF-κB were decreased in turn (all P<0.05).Conclusion　Luteolin can inhibit the activation of TLR4/Syk/NF-κB signal, reduce the oxidative stress and inflammatory injury of retina, and alleviate the retinal injury in ischemia-reperfusion injury rats.

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备注/Memo

备注/Memo:
北京市科学技术委员会科研计划项目（编号：D181100000517009）
更新日期/Last Update: 2021-04-05