| Objective: This subject is based on the good retinal protection effect of Qiming Granules.By establishing a model of radiation retinopathy in rats,we investigated the mechanism of Qiming granules on the intervention of endoplasmic reticulum stress-related protein and HIF1?-VEGF signaling pathway in radiation retinopathy model animals.It provides some ideas and methods for the prevention and treatment of radiation retinal diseases and similar diseases in TCM.Methods: A rat model of radiation retinopathy was established by using linear accelerator to radiate rat eyes.In addition to the normal control group of 25 rats,the remaining 125 rats received radiation,a single dose of 10 Gy,radiation 1 times a week,consecutive 3 weeks,the total dose of30 Gy.Randomly divid into 6 groups: normal group,model group,positive Drug Salubrunal control group(SAL Group),Chinese Medicine high,medium and low dosage group,each group of 25.After 3 months of radiation began to stomach continuously.After 1,3,and 6 months of treatment,Hematoxylin-eosin was used to observe the morphological changes of the retina tissue,and the expression of CHOP,HIF1? and VEGF in retina was detected by immunohistochemical staining.Results:(1)After modeling,compared with the normal control group,observation of Hematoxylin-eosin showed that the retina layers of the model group were loose,and the ganglion cell layer of the model group was disordered with edema,and the cells in each layer were reduced to the inner core layer.And the outer nuclear layer is the mainstay.The retina preparation showed that the capillary arrangement of the model group was disordered and distorted under low magnification,and the thickness of the vascular tubule diameter was not uniform under high magnification,and the number of endothelial cells and pericytes was decreased,and the cells were deformed.Immunohistochemical staining showed that the mean optical density of VEGF increased in the model group,and the difference was obviously significant(P<0.01).Prompt model success.(2)After medication,(1)Hematoxylin-eosin observation display : after one month of drug administration,the number of layers in the middle dose group and the sal group of cells in the Qiming granules was increased.And the morphology is more complete,the ganglion cell layer is arranged more neatly and densely,no obvious edema and vacuole formation.After treatment for 3 months and 6 months,the ganglion cell layer in the middle dose group of Qiming granules was obviously neat,the inner nuclear layer and the outer nuclear layer were relatively intact,and no changes in edema,vascular proliferation,and fiber-enhanced membrane were observed,and there was no obvious difference from the normal group.In the sal group,the inner boundary membrane and retinal fibrous layer cells were slightly proliferated.There was no significant difference between the middle dose group and the middle dose group.It is suggested that Qiming granules can reduce RR retinal edema,improve tissue cell apoptosis,and inhibit the formation of new blood vessels to a certain extent,thereby protecting the changes of morphological changes of the retina.(2)CHOP immunohistochemistry showed :after 1 month,the expression of CHOP protein in the retina of the model group increased,which was significantly different from that of the normal group(P<0.01),and the expression gradually increased with the prolonged administration time;Compared with the model group,the Sal group and the middle-medium dose group showed a decrease in expression after one month of medication(P<0.01),and as the time went on,the expression level continued to decrease toward normal,and the Chinese medicine was low.In the high-dose group,protein expression decreased after 1 month of administration,but it was not statistically significant(P>0.05).As time went by,protein expression decreased significantly(P<0.01).It suggests that the expression of CHOP protein increases in early RR,and the expression increases with time.Traditional Chinese medicine and salubrinal can reduce the expression of CHOP,a protein related to endoplasmic reticulum stress,and the effect is more pronounced with time.(3)HIF-1? immunohistochemistry showed :after 1 month of treatment,the expression of HIF1? protein in the retina of the model group increased,which was significantly higher than that of the normal group(P<0.01).The expression increased with the prolonged administration time.Compared with the model group,the expression of the sal group and the low,middle,and high doses of traditional Chinese medicine decreased,and the difference was obviously significant(P<0.01),but the middle dose of the Chinese medicine was lower than the sal group,and the different was obviously significance(P<0.05).With the prolongation of medication time to March and June,the expression level in the middle-dose group of traditional Chinese medicine decreased continuously,and there was still a statistically significant difference compared with sal(P<0.05).(4)VEGF immunohistochemistry showed:after 1 month,the expression of VEGF protein in the retina of the model group increased,compared with the normal group(P<0.01),and the expression increased continuously with the prolonged administration time;Compared with the model group,expression in the sal group and the low,middle,and high doses of the Chinese herbs all decreased,and the different was obviously significance(P<0.01).Compared with the sal,the high and medium doses of the Chinese herbs increased,and there was no statistical difference.The significance of the study(P>0.05),with the prolonged use of the drug to 3 and 6months,the Chinese medicine dose group than the sal group expression decreased,the difference was no obvously significance(P> 0.05).It is suggested that both salubrinal and Qiming granules can intervene early in the early radioretinopathy HIF-1?-VEGF signaling pathway,reduce the expression of HIF-1?,VEGF and the expression decreases with the prolonged administration time.Conclusion: Qiming granules intervene in early RR retinal injury,reduce retinal tissue edema,inhibit vascular hyperplasia to a certain extent,and have a certain degree of protective effect on retinal tissue cell radiation damage.The mechanism may be through intervention of the intracellular network stress-related CHOP protein expression,reduce HIF-1? expression,inhibit retinal VEGF expression,and then improve retinal tissue ischemia and hypoxia and angiogenesis. |
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