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 , 韓佩晏 , 黃棋 ,  呂紅彬

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

Corresponding?author：

呂紅彬, 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

Video：

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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.	李晶艷, 周琦, 呂紅彬.糖尿病早期視網膜神經元退行性病變最新研究進展[J].眼科新進展, 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, 任蘊卓, 段惠軍, 等.叔丁基對苯二酚對DM小鼠腎臟氧化應激損傷及Nrf2蛋白表達的影響[J].中國藥理學通報, 2009, 25(10):1341-1344.
6.	邵俊偉, 蔡遜.高脂飲食聯合鏈脲佐菌素建立2型DM大鼠模型的研究進展[J].中國實驗動物學報, 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, 呂紅彬, 等. 5, 6-二氫環戊烯并1, 2-二硫雜環戊烯-3-硫酮對2型糖尿病大鼠視網膜核因子NF-E2相關因子及血紅素氧合酶-1表達的影響[J].中華眼底病雜志, 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. 李晶艷, 周琦, 呂紅彬.糖尿病早期視網膜神經元退行性病變最新研究進展[J].眼科新進展, 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, 任蘊卓, 段惠軍, 等.叔丁基對苯二酚對DM小鼠腎臟氧化應激損傷及Nrf2蛋白表達的影響[J].中國藥理學通報, 2009, 25(10):1341-1344.
6. 邵俊偉, 蔡遜.高脂飲食聯合鏈脲佐菌素建立2型DM大鼠模型的研究進展[J].中國實驗動物學報, 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, 呂紅彬, 等. 5, 6-二氫環戊烯并1, 2-二硫雜環戊烯-3-硫酮對2型糖尿病大鼠視網膜核因子NF-E2相關因子及血紅素氧合酶-1表達的影響[J].中華眼底病雜志, 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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