| Objective:Our study was designed to investigate the intervention effects of Jiawei Linggui Zhugan Decoction（JLZD）on clinical characteristics,retinal inflam-mation and oxidative damage caused by acute exposure to plateau in rats and explore the TCM pathological characteristics of high altitude-induced retinal impairment.Methods:SD rats were randomly divided into blank group（2200m）,plateau group（4270m）and JLZD intervention group（4270m）.JLZD intervention group was given JLZD Decoction by gavage once a day for 7 days,while blank group and pla-teau group were given normal saline intragastrically.Average daily food and water intake of rats in each group were recorded every day and the body weight changes of12 rats in each group was measured on 1 d,3 d,5 d and 7 d following acute exposure to the plateau.Bilateral eyeballs were removed and retinas were collected after ex-posure to high altitude for 7 days.The expression of nuclear factor-κB p65（NF-κB p65）in the retina was detected by immunohistochemistry.The m RNA relative ex-pression levels of hypoxic inducible factor-1α（HIF-1α）,NF-κB and tumor necrosis factor-α（TNF-α）were measured by real-time fluorescence quantitative PCR（Rt-PCR）.Enzyme-linked immunosorbent assay（ELISA）was performed to deter-mine the protein concentrations of interleukin-6（IL-6）and interleukin-1β（IL-1β）.Colorimetric method（WST-1,TBA）was conducted to analyze the activity of super-oxide dismutase（SOD）and the content of malondialdehyde（MDA）in rat retina.Results:（1）Average daily food and water intake was significantly decreased both in the plateau group and JLZD intervention group compared to the blank group after 2 days of acute exposure to the plateau（all P<0.05）.Exposure to high altitude for 3 and 7 days the plateau group reduced food intake,which was significantly dif-ferent from that of JLZD intervention and the blank group（all P<0.05）,but there was no difference between JLZD intervention and the blank group（P>0.05）.Re-duced water intake was found both in the plateau group and JLZD intervention group after the plateau exposure for 3 and 4 days when compare to the blank group（all P<0.05）;Exposure to the plateau for 5 days to 7 days the plateau group resulted in a decrease in water intake compared to JLZD intervention group and the blank group（all P<0.05）,but there was no significant difference between JLZD interven-tion group and the blank group（P>0.05）.After 3 days stay in the plateau,the weight of the plateau group was lower than the blank group（P<0.05）;Plateau hypoxia re-duced the body weight of rats in the plateau group following 5 days and 7 days of plateau exposure in comparison with blank group and JLZD intervention group（all P<0.05）,but there was no difference between the JLZD intervention group and the blank group（P>0.05）.After 7 days exposure to the plateau,75.00%of the rats in the plateau group had lingual substance and the score for evaluating the fundal vein reached grade 2,which had statistical difference compared with the JLZD interven-tion group and the blank group（all P<0.01）,no significant difference was seen be-tween the JLZD intervention and the blank group（P>0.05）.（2）The relative expres-sion levels of HIF-1α（1.001±0.132）m RNA and the content of oxidative stress factor MDA[（0.815±0.453）μmol·gprot-1]in retinal tissue of rats in the plateau group were significantly higher than those in the blank group HIF-1αm RNA（0.781±0.128）and MDA[（0.270±0.071）μmol·gprot-1]after 7 days stay in high altitude（all P<0.01）,the antioxidant enzyme SOD[（75.649±7.239）U·mgprot-1]activity was notably de-creased compared with blank group SOD[（122.348±28.615）U·mgprot-1]activity（P<0.01）;The plateau environment upregulated the relative m RNA expression levels of NF-κB,TNF-α（1.284±0.282,4.493±1.410）and the contents of IL-6 and IL-1β[（32.765±5.269,55.644±13.150）pg·m L-1]in the rat retina when compared with those in the blank group NF-κB,TNF-αm RNA（0.845±0.075,1.159±0.864）and IL-6,IL-1β[（24.860±3.458,37.407±2.363）pg·m L-1]（all P<0.01）;The expression of NF-κB p65 in plateau group was stronger than that in blank group.In comparison with the plateau group,JLZD intervention suppressed the relative m RNA expression of HIF-1α（0.805±0.105）（P<0.05）and NF-κB,TNF-α（0.946±0.168,1.976±0.460）（all P<0.01）,lowered the content of MDA[（0.396±0.049）μmol·gprot-1]and cytokine levels of IL-6 and IL-1β[（26.097±2.160,37.638±3.305）pg·m L-1]（all P<0.01）.SOD[（102.370±17.283）U·mgprot-1]activity was notably enhanced in rat retina of JLZD group as compared with the plateau group（P<0.01）.The immunochemical expres-sion of NF-κB p65 in rat retina in the JLZD intervention group was weaker than that in the plateau group.Conclusion:（1）Acute exposure to plateau induces retinal oxidative damage by activating NF-κB/HIF-1αsignaling pathway to overexpress inflammatory cytokines in rat retina.（2）JLZD inhibits the excessive release of retinal inflammatory factors and reduces the damage of retinal oxidative stress by regulating NF-κB/HIF-1αsig-naling pathway.（3）High altitude-induced retinal oxidative damage in rats following acute exposure to the plateau has the pathological characteristics of Qi deficiency and phlegm-blood stasis syndrome. |
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