[1]孟 宏,王桂青,杜竹君.西红花苷通过调控TLR4/MyD88/NF-κB通路改善糖尿病大鼠视网膜病变机制研究[J].陕西医学杂志,2023,52(5):531-535,540.[doi:DOI:10.3969/j.issn.1000-7377.2023.05.008]
　MENG Hong,WANG Guiqing,DU Zhujun.Mechanism of crocin improving diabetic retinopathy by regulating TLR4/MyD88/NF-κB pathway in rats[J].,2023,52(5):531-535,540.[doi:DOI:10.3969/j.issn.1000-7377.2023.05.008]
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西红花苷通过调控TLR4/MyD88/NF-κB通路改善糖尿病大鼠视网膜病变机制研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
52
期数:
2023年5期
页码:
531-535,540
栏目:
基础研究
出版日期:
2023-05-05

文章信息/Info

Title:
Mechanism of crocin improving diabetic retinopathy by regulating TLR4/MyD88/NF-κB pathway in rats
作者:
孟 宏; 王桂青; 杜竹君
(邯郸市中心医院,河北 邯郸 056000)
Author(s):
MENG Hong; WANG Guiqing; DU Zhujun
(Handan Central Hospital,Handan 056000,China)
关键词:
西红花苷;  糖尿病视网膜病变;  视网膜厚度;  血管通透性;  TLR4/MyD88/NF-κB通路;  炎症
Keywords:
Crocin;  Diabetic retinopathy;  Retinal thickness;  Vascular permeability;  TLR4/MyD88/NF-κB pathway;  Inflammation
分类号:
R 285.5
DOI:
DOI:10.3969/j.issn.1000-7377.2023.05.008
文献标志码:
A
摘要:
目的:探讨西红花苷对糖尿病大鼠视网膜病变的影响,并基于Toll样受体4(TLR4)/髓样分化因子88(MyD88)/核转录因子-κB(NF-κB)通路探索其机制。方法:采用高糖高脂饲料喂养+腹腔注射(IP)链脲佐菌素的方法制备糖尿病视网膜病变(DR)大鼠模型,设模型组、西红花苷组、瑞沙托维(TLR4抑制剂)组和西红花苷+瑞沙托维组,每组20只。另取20只大鼠设为正常组。西红花苷组IP给药30 mg/kg,瑞沙托维组IP给药3 mg/kg,西红花苷+瑞沙托维组IP给药30 mg/kg+3 mg/kg,1次/d。12周后,通过光学相干断层扫描检测视网膜厚度,伊文思蓝渗透实验检测视网膜血管通透性,HE染色行视网膜病理学检查,透射电子显微镜观察视网膜细胞超微结构改变,酶联免疫吸附实验(ELISA)检测视网膜肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、IL-8、可溶性细胞间黏附分子1(sICAM-1)含量,Western blot法检测TLR4、MyD88、总NF-κB p65、胞核NF-κB p65、高迁移率族蛋白B1(HMGB1)蛋白表达。结果:与模型组比较,西红花苷组、瑞沙托维组和西红花苷+瑞沙托维组视网膜厚度升高、血管通透性降低(均P<0.05); 视网膜组织病变明显减轻,视网膜感受器内外节层及内外核层细胞超微结构病变明显改善; 视网膜TNF-α、IL-1β、IL-8、sICAM-1含量显著降低,TLR4、MyD88、胞核NF-κB p65、HMGB1相对表达量和胞核NF-κB p65/总NF-κB p65比值降低(均P<0.05)。西红花苷+瑞沙托维组对DR大鼠各指标的影响明显优于西红花苷组和瑞沙托维组(均P<0.05)。结论:西红花苷可降低DR大鼠视网膜血管通透性,减轻视网膜组织病变和细胞超微结构病变,其机制可能与抑制TLR4/MyD88/NF-κB通路和NF-κB核转位,减少促炎因子释放有关。
Abstract:
Objective:To explore the effect of crocin on retinopathy in diabetes rats,and to explore its mechanism based on toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)pathway.Methods:The diabetic retinopathy(DR)rat model was established by feeding the rats with high-sugar and high-fat diet and intraperitoneal injection(ip)of streptozotocin.The rats were divided into model group,crocin group,resatovir group(TLR4 inhibitor)and crocin + resatovir group,with 20 rats in each group.Another 20 rats were taken as normal group.The crocin group was given 30 mg/kg by IP,the resatorvid group was given 3 mg/kg by IP,and the crocin+rosatovir group was given 30 mg/kg+3 mg/kg by IP,once a day. After 12 weeks,the retinal thickness was measured by optical coherence tomography,the retinal vascular permeability was measured by evans blue penetration test,the retinal pathology was examined by HE staining,the ultrastructural changes of retinal cells was observed by transmission electron microscopy,the contents of TNF-α,IL-1β,IL-8,sICAM-1 in retinal tissues were detected by ELISA method,the expressions of TLR4,MyD88,total NF-κB p65,nuclear NF-κB p65,HMGB1 were detected by Western blot.Results:Compared with the model group,the retinal thickness of crocin group,resatorvid group and crocin+resatorvid group was increased,the vascular permeability was decreased(all P<0.05).The pathological changes were significantly improved; the ultrastructural changes of the cells in the inner and outer ganglion layer,the inner and outer nuclear layer of retina were significantly improved.The contents of TNF-α,IL-1β,IL-8,sICAM-1 in retinal tissues were decreased,the expressions of TLR4,MyD88,nuclear NF-κB p65,HMGB1 and the ratio of nuclear NF-κB p65/total NF-κB p65 were decreased(all P<0.05).The effects of crocin+resatorvid group on above indexes of DR rats were significantly better than those of crocin group and resatorvid group(all P<0.05).Conclusion:Crocin can reduce retinal vascular permeability,reduce retinal tissue damage and cell ultrastructure damage in DR Rats,which may be related to inhibiting the TLR4/MyD88/NF-κB pathway and nuclear translocation of NF-κB,and reducing the release of pro-inflammatory factors.

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备注/Memo

备注/Memo:
基金项目:河北省医学科学研究课题(20201541)
更新日期/Last Update: 2023-05-05