| 摘要: |
| 目的：通过缺氧诱导因子（HIF-1）蛋白含量及基因的表达探讨杞黄颗粒对脉络膜新生血管（CNV）发生发展过程的作用机制。方法：健康雄性BN大鼠81只，随机选取13只作为空白对照组，另68只右眼通过激光光凝方式建立CNV模型。光凝7d后随机选取3只检验造模是否成功，余下65只随机分为5组：模型对照组、杞黄颗粒A组、杞黄颗粒B组、雷珠单抗组、杞黄颗粒+雷珠单抗组，各13只。治疗结束后，除杞黄颗粒B组在治疗的第90天处死，其余组大鼠均在治疗的第60天心脏灌注处死，取右眼制作标本，采用Western-blotting和RT-PCR检测HIF-1的蛋白含量及mRNA表达。结果：模型大鼠于激光后第7天OCT检查可见视网膜色素上皮复合层不连续，局部增厚，反射增强，界限不清，眼底荧光血管造影检查显示出少量圆盘状荧光渗漏，表明造模成功。与空白对照组比较，模型对照组HIF-1蛋白和其mRNA的表达趋势一致，均有上调，差异有统计学意义（P<0.05）。HIF-1蛋白表达量，模型对照组明显高于杞黄颗粒+雷珠单抗组，差异有统计学意义（P<0.01）；杞黄颗粒A组、雷珠单抗组、模型对照组组间比较，差异均无统计学意义（P>0.05）；杞黄颗粒B组与A组比较，差异有统计学意义（P<0.05）。HIF-1mRNA表达，模型对照组明显高于雷珠单抗组、杞黄颗粒+雷珠单抗组，杞黄颗粒A组表达高于雷珠单抗组和杞黄颗粒+雷珠单抗组，差异均有统计学意义（P＜0.05）；杞黄颗粒+雷珠单抗组优于雷珠单抗组，但差异无统计学意义（P>0.05）；杞黄颗粒B组与A组比较，差异有统计学意义（P<0.05）。结论：杞黄颗粒联合雷珠单抗在抑制CNV中下调HIF-1蛋白含量及基因表达效果较单纯应用杞黄颗粒更加稳定，长期应用杞黄颗粒对抑制CNV有临床意义，其作用机制可能与下调HIF-1因子有关。 |
| 关键词: 脉络膜新生血管 黄斑变性 BN大鼠 杞黄颗粒 HIF-1 实验研究 |
| DOI： |
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| Interventional effect of Qihuang granules on protein and mRNA expression of hypoxia-inducible factor-1 in experimental choroidal neovascularization |
| WANG Ying-ying，,LIANG Feng-ming，,WANG Li |
| (The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine，Tianjin 300193，China) |
| Abstract: |
| Objective：To investigate the mechanism of action of Qihuang granules in choroidal neovascularization（CNV） by measuring the protein and mRNA expression of hypoxia-inducible factor-1（HIF-1）.Methods：A total of 81 healthy male BN rats were selected，among which 13 were randomly selected as blank control group and 68 were treated with laser photocoagulation for the right eye to establish a model of CNV.After 7 days of photocoagulation，3 rats were randomly selected to evaluate whether the model was successfully established；the remaining 65 rats were randomly divided into model control group，Qihuang granule group A，Qihuang granule group B，ranibizumab group，and Qihuang granule+ranibizumab group，with 13 rats in each group.After the treatment ended，the rats in the Qihuang granule group B were sacrificed on day 90 of treatment，and the other rats were sacrificed on day 60 of treatment by cardiac perfusion.The right eye was collected，and Western blot and RT-PCT were used to measure the protein and mRNA expression of HIF-1.Results：On day 7 after laser photocoagulation，the rats in the model showed discontinuity，local thickening，enhanced reflex，and unclear boundaries of the retinal pigment epithelium on optical coherence tomography and a small amount of disc-shaped fluorescence leakage on fundus fluorescein angiography，suggesting that the model was successfully established.Compared with the blank control group，the model control group had significant increases in the protein and mRNA expression of HIF-1（P<0.05）.The model control group had significantly higher protein expression of HIF-1 than the Qihuang granule+ranibizumab group（P<0.01）；there was no significant difference between the Qihuang granule group A，the ranibizumab group，and the model control group（P>0.05），while there was a significant difference between the Qihuang granule group B and the Qihuang granule group A（P<0.05）.The model control group had significantly higher mRNA expression of HIF-1 than the ranibizumab group and the Qihuang granule+ranibizumab group，and the Qihuang granule group A had significantly higher expression than the ranibizumab group and the Qihuang granule+ranibizumab group（P<0.05）；the Qihuang granule+ranibizumab group had slightly better results than the ranibizumab group（P>0.05）；there was a significant difference between the Qihuang granule group B and the Qihuang granule group A（P<0.05）.Conclusion：Compared with Qihuang granules alone，Qihuang granules combined with ranibizumab has a more stable effect in downregulating the protein and mRNA expression of HIF-1 to inhibit CNV.Long-term application of Qihuang granules has a certain clinical effect in inhibiting CNV，possibly by downregulating HIF-1. |
| Key words: choroidal neovascularization macular degeneration BN rat Qihuang granule hypoxia-inducible factor-1 experimental study |
