Protective effect of Radix Astragali seu Hedysari compound on rat retinal DNA damage induced by acute hypobaric hypoxia

Objective

To investigate the rat retinal DNA damage induced by acute hypobaric hypoxia and the protective effect of Radix Astragali seu Hedysari compound on it.

Methods

Seventy-two healthy clean grade male Sprague Dawley (SD) rats were randomly divided into normal oxygen control group, hypoxic model group and Radix Astragali seu Hedysari compound gavage group by computer random number distribution, with 24 rats in each group.The rats in the normal oxygen control group were fed in normal condition, while the rats in the hypoxic model group and Radix Astragali seu Hedysari compound gavage group were fed in a hypobaric oxygen chamber, which simulated an altitude of 5 kilometers, and the rats were administered intragastrically with Radix Astragali seu Hedysari compound (0.1 g/kg) or the same volume of normal saline once a day according to grouping.Retinal tissue was obtained on the 7th day of continuous administration of drugs after the rats were sacrificed by euthanasia.Histopathological staining was performed to observe the pathological morphology of retina in each group.Immunohistochemistry was used to identify the expressions of p53 and histone family 2A variant ( γH2AX). Real time-PCR was used to determine the relative expression levels of 8-oxoguanine nucleoside triphosphatase (MTH1) and 8-hydroxyguanine glycolsylase (OGG1) mRNA.The use and care of the animals followed Regulations of the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.

Results

The retina of hypoxic model group was thicker than that of the normal oxygen control group and Radix Astragali seu Hedysari compound gavage group, especially the nerve fiber layer and the ganglion cell layer.The positive staining intensities of p53 and γH2AX were stronger in the retinas of the hypoxic model group than those in the the normal oxygen control group and Radix Astragali seu Hedysari compound gavage group.The relative expression levels of MTH1 and OGG1 mRNA in the hypoxic model group were 0.573±0.081 and 0.772±0.136, which were significantly lower than 0.846±0.160 and 1.013±0.168 in the normal oxygen control group, respectively (both at P<0.05). The relative expression level of MTH1 mRNA was 0.748±0.114 in the Radix Astragali seu Hedysari compound gavage group, significantly higher than that in the hypoxic model group (P<0.05). No significant difference was detected in OGG1 mRNA expression level between the Radix Astragali seu Hedysari compound gavage group and the hypoxic model group (P=0.743).

Conclusions

The intervention of Radix Astragali seu Hedysari compound plays a protective role in hypobaric hypoxia-induced retinal DNA damage through modulating the expression of p53, γH2AX, OGG1 and MTH1.