Rhodiola's effect on tissue morphology and hypoxia-inducible factor-1α expression of rat retina in the simulated high altitude hypoxia_Chinese Journal of Ocular Fundus Diseases

Authors：

HuangHaixiang ,  ZhangWenfang , YangYi , 独刚 , 顾倬

Department of Ophthalmology, The Second Hospital of Lanzhou University, Lanzhou 730000, China;

Corresponding author：

ZhangWenfang, Email: zhwenf888@163.com

Keywords：

Retina/physiopathology; RHODIOLA SACRA/therapeutic use; Altitude; Anoxia; Animal experimentation

DOI：

10.3760/cma.j.issn.1005-1015.2014.06.015

Video：

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Objective To observe the effects of Rhodiola on the rat retinal tissue morphology and the hypoxia-inducible factor (HIF)-1α at simulated hypoxia at different altitudes. Methods Forty-eight adult female Sprague Dawley rats were randomly divided into the Rhodiola Intervention group (intervention group) and the control group, each group had 24 rats. The intervention group rats were treated with intraperitoneal injection of 10 ml/kg of large plants Rhodiola solution, and the control group rats were injected with same volume of saline. One hour after the injection, six rats were randomly selected from both of the two groups and reared in the plateau environment simulation laboratory modules with the oxygen partial pressure of 17.4, 14.6, 11.3 and 7.4 kPa, which simulated the altitudes of 1500, 3000, 5000 and 8000 meters indoor respectively. Six hours later the rat eyeballs were harvested for paraffin sections and analyzed by hematoxylin and eosin staining, and immunohistochemical staining to observe the expression of HIF-1α and p53. Results In the control group, the rat retinal layers were edema and loose, the retinal thickness increased, the retinal structure was disorganized, the ganglion cells were swollen and degenerated, and some can observe the karyopyknosis, karyolysis and the reduced cells number. As the altitude increased, the pathological changes of retinal became more obvious. In the intervention group, the characteristics of rat retinal morphology were same with the control group, while the degree of morphology changes was lighter than the control group. HIF-1α and p53 expressed mainly in the ganglion cell layer and inner nuclear layer of rat retina in the control group. As altitude increased, the expression of HIF-1α and p53 were increased too, which was positive correlated (r=0.9846, P < 0.05). Compared with the control group, the rat retinal expression of HIF-1α increased, while expression of p53 decreased in the intervention group, and the differences were statistically significant (P < 0.05). Conclusion Rhodiola can reduce the retinal tissue pathology damage caused by high altitude hypoxia, and its mechanism may be related to the increasing expression of HIF-1α and reducing expression of p53.

Citation： HuangHaixiang, ZhangWenfang, YangYi. Rhodiola's effect on tissue morphology and hypoxia-inducible factor-1α expression of rat retina in the simulated high altitude hypoxia. Chinese Journal of Ocular Fundus Diseases, 2014, 30(6): 599-603. doi: 10.3760/cma.j.issn.1005-1015.2014.06.015 Copy

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1. Jha KN. High altitude and the eye[J]. Asia Pac J Ophthalmol, 2012, 1:166-169.
2. Schmid T, Zhou J, Brüne B. HIF-1 and p53:communication of transcription factors under hypoxia[J]. Cell Mol Med, 2004, 8:423-431.
3. Panossian A, Wikman G, Salxis J. Rosenroot(Rhodiola rosea):traditional use, chemical composition, phammcology and clinical efficacy[J]. Phytomedicine, 20l0, 17:481-493.
4. Vinogradov VI. An experimental model of hypoxic edema of the brain[J]. Patol Fiziol Eksp Ter, 1967, 11:66.
5. Guo P, Luo H, Fan Y, et al. Establishment and evaluation of an experimental animal model of high altitude cerebral edema[J]. Neurosci Lett, 2013, 547:82-86.
6. Ma HP, Wu JH. Establishment of an animal model for acute mountain sicknesswith A decompression chamber[J]. Pharmac J PLA, 2013, 29:301-304.
7. Pokroy R, Tendler Y, Pollack A, et al. p53 expression in the normal murine eye[J]. Invest Ophthalmol Vis Sci, 2002, 43:1736-1741.
8. Semenza GL. Hypoxia-inducible factors in physiology and medicine[J]. Cell, 2012, 148:399-408.
9. Vuong L, Conley SM, Al-Ubaidi MR. Expression and role of p53 in the retina[J]. Invest Ophthalmol Vis Sci, 2012, 53:1362-1371.
10. Pires IM, Bencokova Z, Milani M, et al. Effects of acute versus chronic hypoxia on DNA damage responses and genomic instability[J]. Cancer Res, 2010, 70:925-935.
11. Liu MC, Zhang DJ. The progress of Rhodiola Rosea's pharmacological effects research[J].Asia-Pac Trad Med, 2013, 9:65-69.
12. Xu MC, Shi HM, Wang H, et al. Salidroside protects against hydrogen peroxide-induced injury in HUVECs via the regulation of REDD1 and mTOR activation[J]. Mol Med Rep, 2013, 8:147-153.
13. 黎明华, 汤长发, 欧阳江琼.红景天苷对运动后自由基和能量代谢改变的影响[J].中国应用生理学杂志, 2012, 28:53-56.
14. Wang S, He H, Chen L, et al.Protective effects of salidroside in the MPTP/MPP+-induced model of parkinson's disease through ROS-NO-related mitochondrion pathway.Mol Neurobiol, 2014, 7:E1.[2014-06-27]http://link.springer.com/article/10.1007%2Fs12035-014-8755-0.[published online ahead of print].
15. Li X, Sipple J, Pang Q, et al. Salidroside stimulates DNA repair enzyme Parp-1 activity in mouse HSC maintenance[J]. Blood, 2012, 119:4162-4173.
16. Zhang J, Liu A, Hou R, et al. Salidroside protects cardiomyocyte against hypoxia-induced death:a HIF-1alpha-activated and VEGF-mediated pathway[J]. Eur J Pharmacol, 2009, 607:6-14.
17. Chen X, Zhang Q, Cheng Q, et al. Protective effect of salidroside against H₂O₂-induced cell apoptosis in primary culture of rat hippocampal neurons[J]. Mol Cell Biochem, 2009, 332:85-93.
18. Zheng KY, Zhang ZX, Guo AJ, et al. Salidroside stimulates the accumulation of HIF-1α 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, 679:34-39.

Chinese Journal of Ocular Fundus Diseases

Rhodiola's effect on tissue morphology and hypoxia-inducible factor-1α expression of rat retina in the simulated high altitude hypoxia

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