丹红化瘀口服液对视网膜缺血再灌注损伤大鼠视网膜中央静脉阻塞症的保护作用及机制研究  

Protective effect and mechanism of Danhong Huayu Oral Liquid on central retinal vein occlusion of rats with retinal ischemia-reperfusion injury

作　　者：王玉丽[1,2,3] 林娟 李新[1,2] 郭海彪 徐旭[1,2] 许浚[1,2,5] 李楚源[4] 张铁军[1,2] WANG Yu-li;LIN Juan;LI Xin;GUO Hai-biao;XU Xu;XU Jun;LI Chu-yuan;ZHANG Tie-jun(Tianjin Key Laboratory of Quality Marker of Traditional Chinese Medicine,Tianjin Institute of Pharmaceutical Research,Tianjin 300462,China;State Key Laboratory of Drug Delivery Technology and Pharmacokinetics,Tianjin Institute of Pharmaceutical Research,Tianjin 300462,China;Institute of Chemical Engineering,Tianjin University,Tianjin 300350,China;Guangzhou Baiyunshan Hutchison Whampoa Chinese Medicine Co.,Ltd.,Guangzhou 510515,China;Research Unit for Drug Metabolism,Chinese Academy of Medical Sciences,Tianjin Institute of Pharmaceutical Research,Tianjin 300462,China)

机构地区：[1]天津药物研究院天津市中药质量标志物重点实验室,天津300462 [2]天津药物研究院释药技术与药代动力学国家重点实验室,天津300462 [3]天津大学化工学院,天津300350 [4]广州白云山和记黄埔中药有限公司,广东广州510515 [5]天津药物研究院中国医学科学院药物代谢新技术创新单元,天津300462

出　　处：《中草药》2022年第6期1621-1627,共7页Chinese Traditional and Herbal Drugs

基　　金：国家重大新药创制专项(2017ZX0910001);广州市科学技术协会2019年“广州市院士专家工作站”建设项目资助(600180);中国医学科学院医学与健康科技创新工程项目资助(2019-I2M-5-020)。

摘　　要：目的研究丹红化瘀口服液对视网膜缺血再灌注损伤大鼠模型视网膜中央静脉阻塞症的保护作用及机制。方法通过对前房加压建立大鼠视网膜缺血再灌注损伤模型,给予阿司匹林和丹红化瘀口服液干预30 d。采用苏木素-伊红(HE)染色法观察大鼠视网膜组织病理变化;采用ELISA法检测大鼠血清中白细胞介素-1β(interleukin-1β,IL-1β)、IL-6、IL-10、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、丙二醛(malondialdehyde,MDA)水平及超氧化物歧化酶(superoxide dismutase,SOD)、过氧化氢酶(catalase,CAT)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)活性;采用免疫组化法检测大鼠视网膜组织缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)、半胱氨酸天冬氨酸蛋白酶-3(cystein-asparate protease-3,Caspase-3)、血管内皮生长因子(vascular endothelial grown factor,VEGF)和核因子-κB(nuclear factor-κB,NF-κB)p65蛋白表达情况。结果模型组大鼠视网膜结构紊乱,神经节细胞层细胞减少,视网膜萎缩变薄;丹红化瘀口服液组大鼠视网膜组织结构及神经节细胞变性程度均有所改善。与模型组比较,丹红化瘀口服液组大鼠血清SOD、GSH-Px及CAT活性明显升高(P<0.05、0.01),血清MDA水平显著降低(P<0.05);血清IL-1β、IL-6和TNF-α水平显著降低(P<0.05、0.01),IL-10水平显著升高(P<0.05、0.01);视网膜组织HIF-l、Caspase-3、NF-κB p65和VEGF阳性表达均显著降低(P<0.05)。结论丹红化瘀口服液对视网膜缺血再灌注损伤大鼠的视网膜结构具有改善作用,对神经节细胞具有保护作用,其作用机制可能与抑制视网膜组织细胞凋亡、抗炎和抑制新生血管生成有关。Objective To study the protective effect and mechanism of Danhong Huayu Oral Liquid(丹红化瘀口服液)on central retinal vein occlusion of rats with retinal ischemia-reperfusion injury.Methods A rat model of retinal ischemia-reperfusion injury was established by pressurizing the anterior chamber,and rats were given aspirin and Danhong Huayu Oral Liquid for 30 d.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of retina in rats;ELISA method was used to detect interleukin-1β(IL-1β),IL-6,IL-10,tumor necrosis factor-α(TNF-α),malondialdehyde(MDA)levels and superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px)activity in serum;Immunohistochemistry was used to detect hypoxia inducible factor-1(HIF-1),cystein-asparate protease-3(Caspase-3),vascular endothelial growth factor(VEGF)and nuclear factor-κB(NF-κB)p65 protein expressisons in retinal tissue of rats.Results The retinal structure of rats in model group was disordered,cells of ganglion cell layer were reduced,and retina was atrophied and thinned;The retinal tissue structure and degree of ganglion cell degeneration were improved in Danhong Huayu Oral Liquid group.Compared with model group,activities of SOD,GSH-Px and CAT in serum of rats in Danhong Huayu Oral Liquid group were significantly increased(P<0.05,0.01),and MDA level was decreased(P<0.05);IL-1β,IL-6 and TNF-αlevels were significantly decreased(P<0.05,0.01),and IL-10 level was increased(P<0.05,0.01);HIF-1,Caspase-3,NF-κB p65 and VEGF positive expressions in retinal tissue were significantly decreased(P<0.05).Conclusion Danhong Huayu Oral Liquid can improve the retinal structure in rats with retinal ischemia-reperfusion injury,and has a protective effect on ganglion cells,and its mechanism may be related to the inhibition of retinal tissue apoptosis,anti-inflammation and angiogenesis.

关 键 词：丹红化瘀口服液 视网膜缺血再灌注 氧化应激 炎症 新生血管生成 

分 类 号：R285.5[医药卫生—中药学]