Genistein通过JAK2/STAT3信号通路抑制小鼠视网膜新生血管的形成  

Genistein inhibits retinal neovascularization in mice via JAK2/STAT3 pathway

作　　者：李宸宇 孔丽[2] 王文娟[3] 贺荣华 王永瑞 周国宏[3] LI Chenyu;KONG Li;WANG Wenjuan;HE Ronghua;WANG Yongrui;ZHOU Guohong(Department of Ophthalmology,First Clinical College of Shanxi Medical University,Taiyuan 030001,China;Department of Anatomy,Shanxi Medical University;Department of Lacrimal Duct Disease,Shanxi Eye Hospital;Department of Ophthalmology,Tianjin Children’s Hospital;Department of Emergency,Shanxi Eye Hospital)

机构地区：[1]山西医科大学第一临床医学院眼科,太原030001 [2]山西医科大学解剖教研室,太原030001 [3]山西省眼科医院泪道病科 [4]天津市儿童医院眼科 [5]山西省眼科医院急诊科

出　　处：《山西医科大学学报》2020年第8期841-846,共6页Journal of Shanxi Medical University

基　　金：山西省卫生厅科技攻关计划项目(2011057);山西省留学人员科技活动择优资助项目(2017-31)。

摘　　要：目的研究在高氧诱导小鼠视网膜新生血管形成过程中酪氨酸酶抑制剂Genistein的作用及其机制。方法将36只7日龄清洁级C57BL/6J小鼠通过随机数字表法分为4组,分别为正常对照组、模型组、实验对照组和实验组,每组9只小鼠(即18眼)。正常对照组在自然环境中饲养,不予任何处理。于氧体积分数为(75±2)%的密闭氧箱内饲养另外三组,5 d后返回到自然环境中饲养,实验对照组和实验组小鼠于出生第12天分别予玻璃体腔注射二甲基亚砜DMSO和金雀异黄素Genistein各1μl,而模型组不予处理。第17天时,对各组小鼠行视网膜血管荧光造影并铺片,观察视网膜血管的形态,并分别采用real-time PCR法和Western blot法检测各组小鼠视网膜中JAK2、STAT3 mRNA和蛋白的表达水平。结果视网膜血管荧光造影结果显示,正常对照组小鼠视网膜血管走形自然、清晰,未见新生血管;模型组和实验对照组小鼠视网膜血管可以观察到明显的新生血管簇,伴随着血管走形紊乱,其间可见明显的分支、分层现象;实验组小鼠视网膜新生血管簇较少,未见明显的血管分层、分支现象,走形比较自然。高氧诱导下的模型组和实验对照组小鼠视网膜中JAK2和STAT3的mRNA与蛋白的表达水平明显高于正常对照组,实验组小鼠视网膜中JAK2和STAT3的mRNA与蛋白的表达水平则明显低于模型组和实验对照组(均P<0.05)。结论Genistein可能是通过抑制JAK2/STAT3信号通路,进而抑制视网膜新生血管的形成。Objective To investigate the role and mechanism of tyrosinase inhibitor(Genistein)in the formation of retinal neovascularization in mice induced by hyperoxia.Methods Thirty-six 7-day-old clean-grade C57BL/6J mice were randomly divided into normal control group,model group,experimental control group,and experimental group by random number table method,with 9 mice(18 eyes)in each group.The mice in normal control group were reared in the natural environment without any treatment.The mice in the other 3 groups were reared in a closed oxygen box with an oxygen volume fraction of(75±2)%for 5 d and then returned to the natural environment.At 12 d,the mice(12-day-old)were intravitreally injected with 1μl of DMSO and Genistei in experimental control group and experimental group,respectively,and the mice were given no treatment in model group.At 17 d,the retinal vascular fluorescence was performed to observe the morphology of retinal vessels,and real-time PCR and Western blot were used to detect the mRNA and protein expression levels of JAK2 and STAT3.Results Retinal fluorescein angiogram showed that the retinal blood vessels were gentle and clear in normal control group,and no neovascularization was observed.The retinal blood vessels in model group and experimental control group were disordered,stratified and branched,and the neovascularization cluster was distinct.The retinal blood vessels in experimental group were less stratified and branched,the blood vessels were relatively clear,and there were fewer neovascularization clusters.The mRNA and protein expression levels of JAK2 and STAT3 in the retina in model group and experimental control group were significantly higher than those of normal control group and experimental group(all P<0.05).Conclusion Genistein may inhibit the formation of retinal neovascularization by inhibiting the JAK2/STAT3 signaling pathway.

关 键 词：酪氨酸激酶抑制剂 信号通路 视网膜新生血管 

分 类 号：R363[医药卫生—病理学]