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肝X受体激动剂TO901317对糖尿病视网膜病变大鼠视网膜的保护作用
引用本文:丁剑锋,杨炜,李璐,司超. 肝X受体激动剂TO901317对糖尿病视网膜病变大鼠视网膜的保护作用[J]. 眼科新进展, 2021, 0(8): 712-717. DOI: 10.13389/j.cnki.rao.2021.0148
作者姓名:丁剑锋  杨炜  李璐  司超
作者单位:832000 新疆维吾尔自治区石河子市,石河子大学医学院第一附属医院眼科(丁剑锋,杨炜,司超);214000 江苏省无锡市,无锡市第二人民医院眼科(李璐)
摘    要:目的 探讨肝X受体激动剂TO901317对糖尿病视网膜病变(DR)大鼠视网膜的保护作用.方法 取24只健康SPF级SD大鼠,随机分为正常组、模型组、TO901317组,每组各8只.正常组大鼠不做任何处理;模型组、TO901317组大鼠在禁食24 h后测量空腹血糖浓度,腹腔内注射链脲佐菌素60 mg·kg-1,1周后采尾...

关 键 词:糖尿病视网膜病变  肝X受体激动剂  炎症因子  血管内皮生长因子

Protective effect of liver X receptor agonist TO901317 on the retina of rats with diabetic retinopathy
DING Jianfeng1,YANG Wei1,LI Lu1,SI Chao2. Protective effect of liver X receptor agonist TO901317 on the retina of rats with diabetic retinopathy[J]. Recent Advances in Ophthalmology, 2021, 0(8): 712-717. DOI: 10.13389/j.cnki.rao.2021.0148
Authors:DING Jianfeng1  YANG Wei1  LI Lu1  SI Chao2
Affiliation:1.Department of Ophthalmology, the First Affiliated Hospital, Medical College of Shihezi University, Shihezi 832000, Xinjiang Uygur Autonomous Region, China2.Department of Ophthalmology, the Second People’s Hospital of Wuxi, Wuxi 214000, Jiangsu Province, China
Abstract:Objective To investigate the protective effect of liver X receptor agonist TO901317 on the retina of rats with diabetic retinopathy(DR).Methods Twenty-four healthy SPF SD rats were randomly divided into the normal group, model group and TO901317 group, with 8 rats in each group.Rats in the normal group received no treatment, while rats in the model group and TO901317 group were fasting for 24 h and then injected intraperitoneally with 60 mg·kg-1 streptozotocin. One week later, venous blood was drawn from the tail to detect their fasting blood glucose (FBG) concentration.After that, the FBG concentration was measured once a month. If the FBG concentration was higher than 16.7 mmol·L-1 for 24 consecutive weeks, the model would be deemed as established successfully.In the 25th week, rats in the TO901317 group were intravitreally injected with 5 μL TO901317 (3.125 g·L-1) in both eyes, while the rats in the normal group and model group did not receive any treatment during this stage.After the model was constructed successfully, the retinal tissues of rats in each group were taken for HE staining. Based on this, the changes in the retinal morphology and microvessels of rats in each group were observed, and the retinal thickness was measured.The levels of interleukin (IL)-1β and IL-6 in the retina of rats were detected by ELISA; the mRNA relative expression of ABCA1, IL-1β, IL-6 and VEGF in the retina of rats was detected by real-time quantitative PCR;the protein expression of ABCA1, VEGF, IL-1β and IL-6 in the retina of rats were detected by Western blot.Results The retinal tissues of rats in the normal group were closely connected, the cells were morphologically normal and arranged neatly, and the microvascular structure was normal. For rats in the model group and TO901317 group, the inner limiting membrane in the retina was swollen and fractured seriously, and some endothelial cells were protruding from the inner limiting membrane. The retinal thickness of rats in these two groups was significantly increased compared with that of the normal group, and the differences were statistically significant (all P<0.05).The changes in the retinal structure of rats in the TO901317 group were between those of the normal group and model group, and the retinal thickness was significantly decreased compared with that of the model group. The difference was statistically significant (P<0.05). Compared with the normal group, the levels of IL-1β and IL-6 in the retina of rats in the model group were significantly increased, and the differences were statistically significant (all P<0.05).The levels of IL-1β and IL-6 in the retina of rats in the TO901317 group were significantly lower than those in the model group, and the differences were statistically significant (all P<0.05).Compared with the normal group and TO901317 group, the mRNA and protein relative expression of ABCA1 in the retina of rats in the model group was significantly decreased, the mRNA and protein relative expression of IL-1β, IL-6 and VEGF in the retina of rats in the model group was significantly increased, and all the differences were statistically significant (all P<0.05).Conclusion The liver X receptor agonist TO901317 can up-regulate the ABCA1 expression, down-regulate the IL-1β, IL-6 and VEGF expression, and inhibit the retinal inflammation and angiogenesis in DR rats; thus, it has a protective effect on the DR retina.
Keywords:diabetic retinopathy   liver X receptor agonist   inflammatory factors   vascular endothelial growth factor
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