Astragalus injection' effect on the expression of hypoxia-inducible factor-1α and p53 in the retina of rats under hypoxia environment_Chinese Journal of Ocular Fundus Diseases

Authors：

JiaXiyu ¹ ,  LiuQin ² , ZhangShu ² , BaiHuiling ² , DongWen ¹

1. Gansu University of Chinese Medicine, LanZhou 730000, China;
2. Department of Ophthalmology, Gansu Provincial Hospital, LanZhou 730000, China;

Corresponding author：

LiuQin, Email: summliu@126.com

Keywords：

Astragalus membranaceus/drug effects; Anoxia; Hypoxia-inducible factor 1,alpha subunit; Genes,p53; Animal experimentation

DOI：

10.3760/cma.j.issn.1005-1015.2016.04.018

Video：

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Objective To observe the expression and mechanism of hypoxia-inducible factor-1α (HIF-1α) and p53 protein at the altitude of 5000 meter plateau hypoxia environment in rats, as well as the effect of Astragalus injection. Methods Sixty Sprague Dawley rats were randomly divided into the Astragalus injection intervention group and normal saline control group, 30 rats in each group. Astragalus injection group rats were intraperitoneal injected of Astragalus injection (15 ml/kg) before 30 minutes into the plateau environment simulation cabin, normal saline group rats were intraperitoneal injected with the same volume of saline. 30 minutes after injection, rats in each group were reared in the plateau experiment cabin which simulated altitude of 5000 m (oxygen partial pressure 11.3 kPa) for 2, 6, 8, 12, 24 hours, each time period of 6 rats. When get out, the rats were executed immediately and eyes were harvested. Retinal sections were studied by hematoxylin eosin stain, and immunohistochemical method for HIF-1α and p53 expression. Results For control rats, after 2 hours in the cabin, there was edema in retinal layers. HIF-1α and p53 were expressed mainly in the cytoplasm of retinal layers. When the periods in cabin extended, there was atrophy of retinal nerve fiber layer, swelling and degeneration of ganglion cells. The expression of HIF-1α and p53 was increased. Compared with the control group, the intervention group rat had similar but less severe retinal changes, and the expression of HIF-1α and p53 was significantly decreased (P<0.05). Conclusion Astragalus injection can reduce pathological retinal damage in rats at high altitude environment, and its mechanism may be associated with reduced HIF-1α, p53 expression.

Citation： JiaXiyu, LiuQin, ZhangShu, BaiHuiling, DongWen. Astragalus injection' effect on the expression of hypoxia-inducible factor-1α and p53 in the retina of rats under hypoxia environment. Chinese Journal of Ocular Fundus Diseases, 2016, 32(4): 423-427. doi: 10.3760/cma.j.issn.1005-1015.2016.04.018 Copy

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1. Jha KH. High altitude and the eye[J].Asia Pac J Ophthalmol,2012,1(3):166-169.DOI:10.1097/APO.0b013e318253004e.
2. 黄海香,张文芳,杨义,等.红景天对模拟高海拔缺氧的大鼠视网膜组织形态以及缺氧诱导因子表达的影响[J].中华眼底病杂志,2014,30(6):599-603.DOI:10.3760/cma.j.issn.1005-1015.2014.06.015. Huang HX,Zhang WF,Yang Y,et al.Rhodiola's effect on tissue morphology and hypoxia-inducible factor-1α expression of rat retina in the simulated high altitude hypoxia[J].Chin J Ocul Fundus Dis,2014,30(6):599-630.DOI:10.3760/cma.j.issn.1005-1015.2014.06.015.
3. 谢娟,张静,戎小平,等.缺氧诱导因子及其靶基因血红素加氧酶的研究现状[J].现代中西医结合杂志,2011,20(24):3109-3011.DOI:10.3969/j.issn.1008-8849.2011.24.082. Xie J,Zhang J,Rong XP,et al.Research status of hypoxia-indueible factor and and target genes heme oxygenase[J].Modern Journal of Integrated Traditional Chinese and Western Medicine, 2011, 20(24):3109-3011.DOI:10.3969/j.issn.1008-8849.2011.24.082.
4. 张薇,李若溪,许建华,等.低氧条件下大鼠视网膜HIF-1α及p53的表达及相关分析[J].国际眼科杂志,2006,6(4):795-795.DOI:10.3969/j.issn.1672-5123.2006.04.017. Zhang W,Li RX,Xu JH,et al.Correlation study on expression of HIF-1α and p53 after hypoxia[J].Int Eye Sci,2006,6(4):795-795.DOI:10.3969/j.issn.1672-5123.2006.04.017.
5. Pokroy R,Tendler Y,Pollack A,et al.p53 expression in the normal murine eye[J].Invest Ophthalmol Vis Sci,2002,43(6):1736-1741.
6. 黄海香,张文芳,律鹏.高海拔视网膜病变及中药应用的研究进展[J].国际眼科杂志, 2014, 14(11):1999-2002.DOI:10.3980/j.issn.1672-5123.2014.11.22.DOI:10.3980/j.issn.1672-5123.2014.11.22. Huang HX,Zhang WF,Lyu P.Research progress on high altitude retinopathy and application of Traditional Chinese Medicine[J].Int Eye Sci,2014,14(11):1999-2002.DOI:10.3980/j.issn.1672-5123.2014.11.22.
7. 赵奎卿,贺经.黄芪对大鼠视网膜缺血再灌注损伤的影响[J].国际眼科杂志,2006,6(1):1042-1044. DOI:10.3969/j.issn.1672-5123.2006.05.020. Zhao KQ,He J.Effect of Astragalus membranaceus on retina in rats with the damage of retinal ischemia-reperfusion[J].Int Eye Sci,2006,6(1):1042-1044.DOI:10.3969/j.issn.1672-5123.2006.05.020.
8. 黄海香. 红景天对模拟高海拔缺氧的大鼠视网膜的影响[D].兰州:兰州大学,2015. Huang HX. Rhodiola' effect on rat retina in the simulated high altitude hypoxia[D].Lanzhou:Lanzhou University,2015.
9. Dong A,Xie B,Shen J,et al.Oxidative stress promotes ocularneovascularization[J]. J Cell Physiol,2009,219(3):544-552.DOI:10.1002/jcp.21698.
10. Zhang J,Liu A,Hou R,et al.Salidroside protects cardiomyocyte against hypoxia-induced death:a HIF-lalpha-activated and VEGF-mediated pathway[J].Eur J Pharmacol,2009,607(1-3):6-14.
11. Chen X,Zhang Q,Cheng Q,et al.Protective effect of salidroside against H202-induced cell apoptosis in primary culture of rat hippocampal neurons[J].Mol Cell Biochem, 2009, 332(1-2):85-93.DOI:10.1007/s11010-009-0177-3.
12. Zheng KY,Zhang ZX,Gun AJ,et al.Salidroside stimulates the accumulation of HIF-la protein resulted in the induction of EPO expression:a signaling via blocking the degradation pathway in kidney and liver cells[J].Eur J Pharmacol,2012,679(1-3):34-39.DOI:10.1016/j.ejphar.2012.01.027.
13. 葛晓雯,李旭,任长虹,等.p53在细胞缺氧调控中的作用[J].医学分子生物学杂志, 2007, 15(6):518-522.DOI:10.3870/j.issn.1672-8009.2007.06.012. Ge XW,Li X,Ren CH,et al.egulation by P53 during cellular responses to hypoxia[J].J Med Mol Biol,2007, 15(6):518-522.DOI:10.3870/j.issn.1672-8009.2007.06.012.
14. 匡洪宇,康英英,马丽丽,等.黄芪总黄酮对高糖培养下牛视网膜血管周细胞凋亡的影响[J].中国中医药杂志(原中国药医学报),2008,23(3):250-252. Kuang HY,Kang YY,Ma LL,et al.Effect of total flavonoids of Astragalus on apoptosis of cultured bovine retinal capillary pericytes under high glucose[J].CJTCMP,2008,23(3):250-252.
15. 郑敏,杨宏杰, 张丹,等.黄芪提取液清除自由基的实验研究[J].山东中医杂志,2005,23(12):743-745.DOI:10.3969/j.issn.0257-358X.2004.12.022. Zheng M,Yang HJ,Zhang D,et al.Experimental study on the free radical scavenging ability of astragalus membranaceus[J].Shandong Journal of Traditional Chinese Medicine,2005,23(12):743-745.DOI:10.3969/j.issn.0257-358X.2004.12.022.
16. 高峰丽,戚雪.黄芪对大鼠视网膜缺血再灌注损伤中Bcl-2和Bax表达的影响[J].国际眼科杂志, 2012,12(5):826-828.DOI:10.3969/j.issn.1672-5123.2012.05.06. Gao FL,Qi X.Effect of Astragalus acid on Bcl-2 and Bax in rat retina after ischemia-reperfusion injury[J].Int Eye Sci,2012,12(5):826-828.DOI:10.3969/j.issn.1672-5123.2012.05.06.
17. 葛薇,徐哲,刘升强,等.黄芪多糖对急性高眼压诱导大鼠视网膜神经节细胞的保护作用[J].中华实验眼科杂志,2012,30(12):1080-1084.DOI:10.3760/cma.j.issn.2095-0160.2012.12.007. Ge W,Xu Z,Liu SQ,et al.Protective effect of astragalus polysaccharides on retinal ganglion cell in acute ocular hypertension rat model[J].Chin J Exp Ophthalmol,2012,30(12):1080-1084.DOI:10.3760/cma.j.issn.2095-0160.2012.12.007.

Chinese Journal of Ocular Fundus Diseases

Astragalus injection' effect on the expression of hypoxia-inducible factor-1α and p53 in the retina of rats under hypoxia environment

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