The influence of tert-butyl hydroquinone on retinal nuclear factor E2-related factor 2 and heme oxygenase-1 in type 2 diabetic rats_Chinese Journal of Ocular Fundus Diseases

Authors：

LiJingyan , TianMin , ZhangSiyuan , 韩佩晏 , 黄棋 ,  吕红彬

Department of Ophthalmology, The First Affiliated Hospital of Sichuan Medical College, Luzhou 646000, China;

Corresponding author：

吕红彬, Email: oculistlvhongbin@163.com

Keywords：

Diabetic retinopathy/physiopathology; NF-E2-related factor 2; Heme oxygenase (decyclizing); Animal experimentation

DOI：

10.3760/cma.j.issn.1005-1015.2015.06.017

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Objective To observe the effect of tert-butyl hydroquinone (tBHQ) on type 2 diabetic rats retinal nuclear factor E2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1). Methods 60 Sprague Dawley rats were randomly divided into normal control group (NC group, n=20) and model group (n=40). The rats in model group were intraperitoneal injected with streptozotocin (30 mg/kg) to establishing type 2 diabetic mellitus (DM). There were 35 rats successfully established and they were randomly divided into diabetic group (DM group, 17 rats) and tBHQ group (18 rats). The rats in tBHQ group were fed with high fat and sugar diet with 1% tBHQ. After 4 weeks and 12 weeks of tBHQ intervention, hematoxylin eosin staining of retinal sections, immunohistochemical staining and quantitative polymerase chain reaction (PCR) of Nrf2 and HO-1 were performed. Results In tBHQ control, the retina of rats was normal and individual cells showed slightly edema at 4 weeks; the retinal structure of rats was clear and part of cells showed edema at 12 weeks. At 4 and 12 weeks, the expression of Nrf2 (t=3.115, 3.781) and HO-1 (t=3.485, 3.785) protein in DM group were higher than that in NC group (P < 0.05); the expression of Nrf2 (t=2.473, 2.576) and HO-1 (t=2.785, 2.879) protein in tBHQ group were higher than that in DM group (P < 0.05). In DM group, the expression of Nrf2 protein at 12 weeks was higher than that at 4 weeks (t=0.276, P < 0.05). In tBHQ group, the expression of Nrf2 (t=2.516) and HO-1 (t=2.776) protein at 12 weeks were higher than that at 4 weeks (P < 0.05). 4 and 12 weeks, the expression of Nrf2 (t=4.758, 4.285) and HO-1 (t=5.114, 4.514) mRNA in DM group were higher than that in NC group (P < 0.05); the expression of Nrf2 (t=5.133, 4.976) and HO-1 (t=4.758, 4.251) mRNA in tBHQ group were higher than that in DM group (P < 0.05). In DM gruop, the expression of Nrf2 protein at 12 weeks was higher than that at 4 weeks (t=5.114, P < 0.05). In tBHQ group, the expression of Nrf2 (t=4.292) and HO-1 (t=4.974) protein at 12 weeks were higher than that at 4 weeks (P < 0.05). Conclusion tBHQ intervention can increased the expression of Nrf2, HO-1 significantly in the retina of type 2 diabetic rats.

Citation： LiJingyan, TianMin, ZhangSiyuan. The influence of tert-butyl hydroquinone on retinal nuclear factor E2-related factor 2 and heme oxygenase-1 in type 2 diabetic rats. Chinese Journal of Ocular Fundus Diseases, 2015, 31(6): 581-585. doi: 10.3760/cma.j.issn.1005-1015.2015.06.017 Copy

1.	李晶艳, 周琦, 吕红彬.糖尿病早期视网膜神经元退行性病变最新研究进展[J].眼科新进展, 2015, 35(5):493-496.
2.	Xu Z, Wei Y, Gong J, et al. NRF2 plays a protective role in diabetic retinopathy in mice[J]. Diabetologia, 2014, 57(1):204-213.
3.	Agarwal A, Nick HS. Renal response totissue injury: lessons fromheme oxygenase-1 GeneAblation and expression[J]. J Am Soc Nephrol, 2000, 11(5):965-973.
4.	Dreger H, Westphal K, Weller A, et al.Nrf2-depengdent upreglation of antioxidative enzymes: a novel pathway for proteasome inhibitor-mediated cardioprotection [J]. Cardiovasc Res, 2009, 83(2):354-361.
5.	李航, 任蕴卓, 段惠军, 等.叔丁基对苯二酚对DM小鼠肾脏氧化应激损伤及Nrf2蛋白表达的影响[J].中国药理学通报, 2009, 25(10):1341-1344.
6.	邵俊伟, 蔡逊.高脂饮食联合链脲佐菌素建立2型DM大鼠模型的研究进展[J].中国实验动物学报, 2014, 22(4):90-93.
7.	Srinivasan K, Ramarao P.Animal models in type 2 diabetes research: an overview[J].Indian J Med Res, 2007, 125(3):451-472.
8.	Liu XY, Li CY, Bu H, et al. The neufoprotective potential of phaseⅡenzyme inducer on motor neuron survival in traumatic Spina cord injury in vitro[J]. Cell Mol Neurobio, 2008, 28(5):769-779.
9.	Li H, Zhang L, Wang F, et al. Attenuation of glomerular injury in diabetic mice with tert-butylhydroquinone through nuclear factor erythroid 2-related factor 2-dependent antioxidant geneactivation[J]. Am J Nephrol, 2011, 33: 289-297.
10.	He M, Pan H, Xiao C, et al. Roles for redo signaling by NADPH oxidase in hyperglycemia-induced heme oxygenase-1 expression in the diabetic retina[J]. Invest Ophthalmol Vis Sci, 2013, 54(6):4092-4101.
11.	Shen G, Jeong WS, Hu R, et al. Regulation of Nrf2, NF-kappaB, and AP-1 signaling pathways by chemopreventive agents[J].Antioxid Redox Signal, 2005, 7(11-12):1648-1663.
12.	Shih AY, Li P, Murphy TH.A-small-molecule-inducible Nrf2-mediated antioxidant response provides effective prophylaxis against Cerebral ischemia in vivo[J]. J Neurosci, 2005, 25(44):10321-10335.
13.	Chen Y, Wang S, Fu X, et al. tert-Butylhydroquinone mobilizes intracellular-bound zinc to stabilize Nrf2 through inhibiting phosphatase activity[J]. Am J Physiol Cell Physiol, 2015, 309(3):148-158.
14.	田敏, 周琦, 吕红彬, 等. 5, 6-二氢环戊烯并1, 2-二硫杂环戊烯-3-硫酮对2型糖尿病大鼠视网膜核因子NF-E2相关因子及血红素氧合酶-1表达的影响[J].中华眼底病杂志, 2014, 30 (2): 187-192.
15.	Song MY, Kim EK, Moon WS, et al. Sulforaphane protects against cytokine-and streptozotocin-induced beta-cell damage by suppressing the NF-kappaB pathway[J]. Toxicol Appl Pharmacol, 2009, 235(1):57-67.

1. 李晶艳, 周琦, 吕红彬.糖尿病早期视网膜神经元退行性病变最新研究进展[J].眼科新进展, 2015, 35(5):493-496.
2. Xu Z, Wei Y, Gong J, et al. NRF2 plays a protective role in diabetic retinopathy in mice[J]. Diabetologia, 2014, 57(1):204-213.
3. Agarwal A, Nick HS. Renal response totissue injury: lessons fromheme oxygenase-1 GeneAblation and expression[J]. J Am Soc Nephrol, 2000, 11(5):965-973.
4. Dreger H, Westphal K, Weller A, et al.Nrf2-depengdent upreglation of antioxidative enzymes: a novel pathway for proteasome inhibitor-mediated cardioprotection [J]. Cardiovasc Res, 2009, 83(2):354-361.
5. 李航, 任蕴卓, 段惠军, 等.叔丁基对苯二酚对DM小鼠肾脏氧化应激损伤及Nrf2蛋白表达的影响[J].中国药理学通报, 2009, 25(10):1341-1344.
6. 邵俊伟, 蔡逊.高脂饮食联合链脲佐菌素建立2型DM大鼠模型的研究进展[J].中国实验动物学报, 2014, 22(4):90-93.
7. Srinivasan K, Ramarao P.Animal models in type 2 diabetes research: an overview[J].Indian J Med Res, 2007, 125(3):451-472.
8. Liu XY, Li CY, Bu H, et al. The neufoprotective potential of phaseⅡenzyme inducer on motor neuron survival in traumatic Spina cord injury in vitro[J]. Cell Mol Neurobio, 2008, 28(5):769-779.
9. Li H, Zhang L, Wang F, et al. Attenuation of glomerular injury in diabetic mice with tert-butylhydroquinone through nuclear factor erythroid 2-related factor 2-dependent antioxidant geneactivation[J]. Am J Nephrol, 2011, 33: 289-297.
10. He M, Pan H, Xiao C, et al. Roles for redo signaling by NADPH oxidase in hyperglycemia-induced heme oxygenase-1 expression in the diabetic retina[J]. Invest Ophthalmol Vis Sci, 2013, 54(6):4092-4101.
11. Shen G, Jeong WS, Hu R, et al. Regulation of Nrf2, NF-kappaB, and AP-1 signaling pathways by chemopreventive agents[J].Antioxid Redox Signal, 2005, 7(11-12):1648-1663.
12. Shih AY, Li P, Murphy TH.A-small-molecule-inducible Nrf2-mediated antioxidant response provides effective prophylaxis against Cerebral ischemia in vivo[J]. J Neurosci, 2005, 25(44):10321-10335.
13. Chen Y, Wang S, Fu X, et al. tert-Butylhydroquinone mobilizes intracellular-bound zinc to stabilize Nrf2 through inhibiting phosphatase activity[J]. Am J Physiol Cell Physiol, 2015, 309(3):148-158.
14. 田敏, 周琦, 吕红彬, 等. 5, 6-二氢环戊烯并1, 2-二硫杂环戊烯-3-硫酮对2型糖尿病大鼠视网膜核因子NF-E2相关因子及血红素氧合酶-1表达的影响[J].中华眼底病杂志, 2014, 30 (2): 187-192.
15. Song MY, Kim EK, Moon WS, et al. Sulforaphane protects against cytokine-and streptozotocin-induced beta-cell damage by suppressing the NF-kappaB pathway[J]. Toxicol Appl Pharmacol, 2009, 235(1):57-67.

Chinese Journal of Ocular Fundus Diseases

The influence of tert-butyl hydroquinone on retinal nuclear factor E2-related factor 2 and heme oxygenase-1 in type 2 diabetic rats

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