| Purpose:To summarize the changes of eye injury induced by simulated long-term weightlessness in rats,and preliminarily explore the role of ginkgo biloba extract,multivitamin B,folic acid,catalpol,and acupuncture in its mechanism.Methods:1.Literature research on spaceflight-associated neuro-ocular syndromeThrough searching multiple databases of CNKI,WANFANG,VIP,CBM,Pub Med,Embase,Ovid,Web of Science,and Cochrane Library,we can use "space flight","simulated weightlessness","microgravity","eye","space flight","simulated weightlessness","microgravity",and "vision" are keywords to search,require original clinical studies related to the eye in microgravity/simulated weightlessness environment,with clear observation indicators and complete data,enter the research objects,observation time,indicators and main results of the included literature into Excel 2016 respectively,import the included literature into Endnote X9,construct a literature database related to space flight.2.The changes of simulated long-term weightlessness induced eye injury in ratsFifty-five SD rats were randomly divided into a blank group of 10,model 1 with15 rats,model 2 with 15 rats,and model 3 with 15 rats.Each model group adopts the tail suspension method to make models,and the experimental period of each group is set as follows: model 1 group tail suspension for 8 weeks,model 2 group tail suspension for 10 weeks,model 3 group tail suspension for 12 weeks.Observe the changes of intraocular pressure and choroidal thickness before modeling,4 weeks after modeling,and at the end of the experiment.Combine HE staining and transmission electron microscopy to evaluate the morphological and structural changes of rat retina and optic nerve.Iba1,Brn3 a,ARG1,Cas3,CC1 protein and NF-κB,Cas3,Bax/Bcl-2 mRNA expression levels were detected by immunofluorescence and qRT-PCR.3.Exploration of four different interventions in the mechanism of this modelAccording to the principle of random grouping,10 rats in the control group and the remaining 75 rats were divided into the model group,the intervention group 1 was intraperitoneally injected with Ginkgo biloba extract,the intervention group 2 was given by multivitamin B and folic acid,and the intervention group 3 were given catalpol by gavage,intervention 4 groups of acupuncture,15 rats in each group.Through intraocular pressure measurement and OCT examination,the influence of different intervention measures on intraocular pressure and choroidal thickness before,4 weeks,and 12 weeks after the model was analyzed.The optical and electron microscopy were used to detect the changes in retinal thickness and optic nerve structure,and immunity fluorescence,qRT-PCR,and Western blot were used to detect the expression levels of Iba1,Brn3 a,ARG1,Cas3,and other proteins,NF-κB,Cyt c,Cas3,Bax/Bcl-2 mRNA and the expression level of AKT and p-AKT.Results:1.Literature characteristics of spaceflight-associated neuro-ocular syndrome:(1)Microgravity/simulated weightlessness methods mainly include 4 methods,namely head-down tilt simulated weightlessness 67.58%,microgravity(spaceflight)31.58%,parabolic flight method 1.32%,and dry immersion 1.32%.(2)The experimental observation period ranges from the shortest 20 seconds or so to the longest cumulative space flight of 520 days.There are 32 short-term studies(≤14 d)in microgravity/simulated weightlessness(50.00%),and 32 mid-to-long-term studies(50.00%).(3)There are a total of 48 kinds of eye-related physical signs,the most common is the increase in intraocular pressure,followed by the increase in total retinal thickness,choroidal thickness,optic disc edema,and globe flattening.(4)The short-term and mid-to-long-term corresponding eye signs are quite different.All signs of spaceflight-associated neuro-ocular syndrome appear in the mid-to-long-term,short-term only globe flattening,thickening of retinal nerve fiber layer and hyperopic refractive error shifts.2.Features of simulated long-term weightlessness-induced eye damage in rats:(1)Intraocular pressure(IOP): four weeks after modeling,compared with before modeling,the IOP of both eyes of the three models were no difference P>0.05.At the end of the experiment,compared with the blank group,the binocular IOP of the model 3 group was reduced P<0.05;compared with the model 1 group,the right eye IOP of the model 3 group and the left eye IOP of model 2 group were reduced P<0.01;compared with the model 2 group,the binocular intraocular pressure of the model 3group was significantly reduced P<0.001;the binocular intraocular pressure of the left eye of the model 1 group and the model 2 group were increased compared with 4weeks after the model was made P<0.001.Choroidal thickness: four weeks after modeling,compared with before modeling,the choroidal thickness of both eyes of the three models were thickened P<0.05.At the end of the experiment,the binocular choroid of the three model groups was thickened compared with before modeling P<0.05;compared with the blank group,the choroid of the three model groups was thickened P<0.01;compared with four weeks after modeling,the choroid of the model 1 group was thickened P<0.01.(2)HE staining: the retina and optic nerve of each model group showed obvious pathological changes.Compared with the blank group and model 1group,the total retinal of the model 2 group and the model 3 group was thinned.Compared with the blank group,the number ofRGCs in each model group decreased significantly P<0.0001.Transmission electron microscopy: the optic nerve tissues in each model group had different degree of axon swelling and myelin sheath decompaction.Compared with the blank group,the G ratio of the model 3 group decreased P<0.01;compared with the model 1 group,the G ratio of the model 3 group decreased P<0.05.(3)Immunofluorescence: compared with the blank group,the expression of Iba1 in the retina of each model group increased P<0.05,the expression of Brn3 a decreased P<0.05,and the expression of Cas3 increased in the model 2 and model 3groups P<0.0001;compared with the model 1 group,the model 2 group and the model 3 group the expression of Iba1 and Cas3 increased significantly P<0.001,and the expression of Brn3 a in the model 3 group decreased P<0.01.Compared with the blank group,the expression of optic nerve CC1 in each model group decreased P<0.05,and the expression of ARG1,Iba1 and Cas3 increased P<0.01;the expression of Cas3 in the model 2 and model 3 groups increased significantly compared with the model 1 group P<0.0001,compared with the model 2 group the expression of Cas3 in the model 3 group increased P<0.001.(4)qRT-PCR: compared with the blank group,the expression of NF-κB in each model group increased significantly P<0.001;compared with the model 1 group,the expression of the model 2 group and the model 3 group increased significantly P<0.001.Compared with the blank group,the expression of Cas3 in the model 1group increased P<0.01,the model 2 group was significantly increased P<0.001,and the model 3 group was significantly increased P<0.0001;compared with the model 1group,the expression of the model 3 group increased P<0.05.Compared with the blank group,the Bax/Bcl-2 ratio of each model group increased significantly P<0.001,and the model 3 group increased significantly P<0.001 compared with the model 1and model 2 groups.3.The intervention effect of four different measures in this model:(1)Intraocular pressure: four weeks after modeling,compared with the blank group,the IOP of left eye of the intervention group 1 decreased P<0.05,compared with before the modeling,the left eye of the intervention group 1 and the eyes of the intervention group 4 decreased P<0.05.Twelve weeks after modeling,compared with the blank group,the IOP of the left eye of the intervention group 1 and the right eye of the intervention group 2 decreased P<0.05;compared with the model group,the intraocular pressure of the right eye of the intervention group 2 decreased P<0.01;compared with before the modeling,the left eye of the intervention group 1 and the right eye of the intervention group 4 were decreased P<0.05.Choroidal thickness: four weeks after modeling,compared with the model group,intervention 1 group left eye,intervention group 2 left eye,intervention group 4 left eye,and intervention group 3 both eyes,the choroidal thickening of the eyes were reduced P<0.05;twelve weeks after the modeling,compared with the model group,the choroidal thickening of the eyes in the intervention group 1,the eyes in the intervention group 3,and the eyes in the intervention group 4 were reduced P<0.05.In comparison to pre-modeling,the eyes of the model group,the right eye of the intervention group 1,the eyes of the intervention group 3,and the eyes of the intervention group 4,the choroidal thickening P<0.05.(2)HE staining: no obvious pathological changes were seen in each intervention group.Compared with the model group,the total retinal thickness of each intervention group was thickened P<0.001.Compared with the model group,the number ofRGCs in the intervention group 3 increased P<0.05.Transmission electron microscopy: there were no obvious demyelination changes in the optic nerve of each intervention group.Compared with the model group,Gratios that are elevated across intervention groups(P<0.0001 for intervention groups 1and 3,P<0.01 for intervention group 2 and P<0.001 for intervention group 4);compared with the intervention group 2,intervention group 3 G ratio increased P<0.05.(3)Immunofluorescence: compared with the blank group,the expression of Iba1 and Cas3 in the retina of the model group and each intervention group increased significantly P<0.001,and the expression of Brn3 a in the model group decreased P<0.001,and there was no significant change in each intervention group.Compared with the model group,Iba1 and Cas3 in the retina of each intervention group The expression decreased P<0.05,and the Brn3 a expression in the intervention group 1,3and 4 increased P<0.01.Compared with the blank group,the expression of optic nerve CC1 in the model group decreased P<0.05,the expression of AGR1,Iba1,and Cas3 increased significantly P<0.0001,and the expression of Cas3 and ARG1 in each intervention group increased significantly P<0.0001;compared with the model group,CC1 in each intervention group had no Differences,the expression of Cas3 decreased significantly P<0.001,the expression of ARG1 intervention group 1,3 and 4increased P<0.05,the expression of Iba1 evaluated across intervention groups(group1 and 3 P<0.0001,group 4 increased P<0.001,and group 2 P<0.05).(4)qRT-PCR: compared with the blank group,the expression of NF-κB in each intervention group and model group increased significantly P<0.001;compared with the model group,the expression of each intervention group decreased significantly P<0.001.Compared with the blank group,the expression of Cyt c in the model group increased significantly P<0.0001,and in the intervention group 2 increased P<0.05;compared with the model group,each intervention group significantly decreased P<0.0001.Compared with the blank group,the expression of Cas3 in the model group increased P<0.001,and the intervention group 2 increased P<0.01;compared with the model group,the expression of intervention group 1 decreased P<0.001,the expression of intervention group 3 decreased P<0.01,and the expression of intervention group 4 decreased P<0.05.Compared with the blank group,the Bax/Bcl-2 ratio of each intervention group decreased P<0.05;compared with the model group,the ratio of each intervention group decreased P<0.0001;compared with the intervention group 2,the intervention group 1,3,and 4 decreased P<0.05.(5)Western blot: compared with the blank group,the expression of p-AKT/AKT in the model group was down-regulated P<0.05,and the expression of p-AKT/AKT in the intervention group 1 was up-regulated P<0.05;compared with the model group,the expression of p-AKT/AKT in the intervention group 1 significantly up-regulated P <0.0001,the expression of p-AKT/AKT was up-regulated in intervention 2,3,and4 groups P<0.01.Conclusion:1.Short-term and mid-to-long-term microgravity environments have different effects on the structure and function of the human eye.The degree of damage and symptoms are positively correlated with time,and long-term space flight has an irreversible potential risk;there is currently a lack of mid-to-long-term ground research that need attention.2.The degree of simulated long-term weightlessness caused rat eye damage is positively correlated with tail suspension time.At twelve weeks after modeling,the choroidal thickness of the rat was significantly thickened,the optic nerve was demyelinated,brn3 a expression in the retina was reduced,the expression of Iba1 and Cas3 was up-regulated,and the mRNA expression of Bax/Bcl-2 has increased significantly.The damage mechanism may be related to the activation and apoptosis of microglia.3.Ginkgo biloba extract,vitamin B complex and folic acid,catapol,and acupuncture can alleviate the eye damage caused by the model to varying degrees,ginkgo biloba extract has the best intervention effect,followed by catapol.4.Ginkgo biloba extract up-regulates the expression of p-AKT/AKT in a model that simulates long-term weightlessness-induced eye damage in rats,and its protective effect may be related to the activation of the PI3K/AKT pathway to induce antiinflammatory effects. |
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