依那西普对糖尿病大鼠视网膜凋亡通路中Fas,TNF-α及caspase-8表达的影响
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摘要
目的观察依那西普对糖尿病大鼠视网膜细胞凋亡通路中Fas,TNF-α及caspase-8表达的影响,探讨依那西普对糖尿病视网膜病变的治疗作用。方法 SD大鼠随机分为对照组、模型组、治疗组,建立链脲佐菌素(STZ)糖尿病大鼠模型,每周测血糖及体质量。Western-blot法检测大鼠视网膜中Fas,TNF-α及caspase-8的表达,比较各组大鼠视网膜血管伊文思蓝渗漏量。结果治疗组、模型组视网膜的Fas,TNF-α及caspase-8表达均高于对照组(P<0.01),治疗组低于模型组(P<0.01)。治疗组的视网膜伊文思蓝渗漏量低于模型组(P<0.01),治疗组、模型组均高于对照组(P<0.01)。结论依那西普可以有效减少糖尿病大鼠视网膜凋亡通路中Fas,TNF-α及caspase-8的表达,减少糖尿病大鼠视网膜的渗漏量,减轻糖尿病大鼠视网膜病变。
Objective To observe the effect of Etanercept on the expression of Fas, TNF-α, and caspase-8 in the retinal apoptotic pathway in diabetic rats, and to explore the therapeutic effect of etanercept on diabetic retinopathy. Methods SD rats were randomly divided into control group, model group, and treatment group. A streptozotocin(STZ) diabetic rat model was established. The blood glucose and body weight of the model rats were measured every week. Specimens from each group were obtained after 12 weeks of treatment. The expression of Fas, TNF-α, and caspase-8 in rat retina was quantitatively detected by Western-blot, and Evans blue leakage test was used to compare the quantitative determination of retinal vascular leakage in each group of rats. Result The expression of Fas, TNF-α, and caspase-8 with Western-blot in the treatment group was lower than that inthe model group(P<0.01), while in the treatment group and the model group they were higher than that in the control group(P<0.01). The Evans blue leakage test was used to detect the retinal leakage in each group, and it showed the leakage in the treatment group was lower than that in the model group(P<0.01), while in the treatment group and the model group it were higher than that in the control group(P<0.01). Conclusion Etanercept can effectively reduce the expression of Fas, TNF-α, and caspase-8 in the retinal apoptotic pathway of diabetic rats, and it can reduce the leakage of retinal cells in diabetic rats, effectively reduce the retinopathy of diabetic rats as well.
Objective To observe the effect of Etanercept on the expression of Fas, TNF-α, and caspase-8 in the retinal apoptotic pathway in diabetic rats, and to explore the therapeutic effect of etanercept on diabetic retinopathy. Methods SD rats were randomly divided into control group, model group, and treatment group. A streptozotocin(STZ) diabetic rat model was established. The blood glucose and body weight of the model rats were measured every week. Specimens from each group were obtained after 12 weeks of treatment. The expression of Fas, TNF-α, and caspase-8 in rat retina was quantitatively detected by Western-blot, and Evans blue leakage test was used to compare the quantitative determination of retinal vascular leakage in each group of rats. Result The expression of Fas, TNF-α, and caspase-8 with Western-blot in the treatment group was lower than that inthe model group(P<0.01), while in the treatment group and the model group they were higher than that in the control group(P<0.01). The Evans blue leakage test was used to detect the retinal leakage in each group, and it showed the leakage in the treatment group was lower than that in the model group(P<0.01), while in the treatment group and the model group it were higher than that in the control group(P<0.01). Conclusion Etanercept can effectively reduce the expression of Fas, TNF-α, and caspase-8 in the retinal apoptotic pathway of diabetic rats, and it can reduce the leakage of retinal cells in diabetic rats, effectively reduce the retinopathy of diabetic rats as well.
引文
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[15] 胡影影,李全民.糖尿病周围神经病变发病机制的研究进展[J].医学综述,2016,22(20):4050-4053.
[16] Tavares F J,Alves M,Diassantos A,et al.Retinal neurodegeneration in diabetic patients without diabetic retinopathy[J].IOVS,2016,57(14):6455-6460.
[2] Ferrari D,Speciale A,Cristani M,et al.Cyanidin-3-O-glucoside inhibits NF-kB signalling in intestinal epithelial cells exposed to TNF-α and exerts protective effects via Nrf2 pathway activation[J].Toxicol Lett,2016,264:51-58.
[3] Ahsan H.Diabetic retinopathy--biomolecules and multiple pathophysiology[J].Diabetes Metab Syndr,2015,9(1):51-54.
[4] 黄焱,陈少强,陈瑞华,等.川芎嗪对糖尿病大鼠视网膜自由基损伤的保护作用[J].福建医科大学学报,2001,35(2):124-126.
[5] 罗岩,许岭翎,张承芬,等.巴曲酶对糖尿病大鼠血视网膜屏障和视网膜血管内皮生长因子表达的影响[J].中华眼底病杂志,2006,22(1):16-19.
[6] Li Q,Li Z,Zhang S W,et al.Regulation of VEGF of puerarin on STZ diabetic rats retinal and the promoting apoptosis study of puerarin on STZ diabetic rats retinal[J].J Clinical & Experimental Medicine,2017,17:1679-1682.
[7] Navaratna D,Mcguire P G,Menicucci G,et al.Proteolytic degradation of VE-cadherin alters the blood-retinal barrier in diabetes[J].Diabetes,2007,56(9):2380-2387.
[8] 杨柳,王允山,梁浩,等.死亡受体在神经系统疾病中的作用及在神经系统中的下游信号传送机制[J].生命的化学,2010,30(5):723-728.
[9] 潘永露,何淑芳,韩正怡,等.Fas/caspase-8/3和ERK信号通路在Fas siRNA减轻心肌细胞缺氧/复氧损伤中的作用[J].中国药理学通报,2018,34(8):1150-1157.
[10] Pérez de Diego R,Sánchez-Ramón S,López-Collazo E,et al.Genetic errors of the human caspase recruitment domain-B-cell lymphoma 10-mucosa-associated lymphoid tissue lymphoma-translocation gene 1(CBM)complex:molecular,immunologic,and clinical heterogeneity[J].J Allergy Clin Immunol,2015,136(5):1139-149.
[11] Bodiga V L,Thokala S,Vemuri P K,et al.Zinc pyrithione inhibits caspase-3 activity,promotes ErbB1-ErbB2 heterodimerization and suppresses ErbB2 downregulation in cardiomyocytes subjected to ischemia/reperfusion[J].J Inorg Biochem,2015,153:49-59.
[12] Demircan N,Safran B G,Soylu M,et al.Determination of vitreous interleukin-1 (IL-1) and tumour necrosis factor (TNF) levels in proliferative diabetic retinopathy[J].Eye,2006,20(12):1366.
[13] Joussen A M,Doehmen S,Le M L,et al.TNF-alpha mediated apoptosis plays an important role in the development of early diabetic retinopathy and long-term histopathological alterations[J].Mol Vis,2009,15:1418-1428.
[14] Hamid Akash M S,Rehman K,Liaqat A.Tumor necrosis factor-alpha:Role in development of insulin resistance and pathogenesis of type 2 diabetes mellitus[J].J Cell Biochem,2017,119(1):105-111.
[15] 胡影影,李全民.糖尿病周围神经病变发病机制的研究进展[J].医学综述,2016,22(20):4050-4053.
[16] Tavares F J,Alves M,Diassantos A,et al.Retinal neurodegeneration in diabetic patients without diabetic retinopathy[J].IOVS,2016,57(14):6455-6460.