叔丁基对苯二酚(tBHQ)对2型糖尿病大鼠视网膜的长期保护作用  

Long-term protective effect of tert-butyl hydroquinone on the retina of type 2 diabetic rats

作　　者：罗云霞 余曦 田敏 邓偲捷 吕红彬 LUO Yunxia;YU Xi;TIAN Min;DENG Sijie;LV Hongbin(Department of Ophthalmology,Affiliated Hospital of Southwest Medical University,Luzhou 646000,Sichuan Province,China;Department of Ophthalmology,Luzhou Second People’s Hospital,Luzhou 646100,Sichuan Province,China;Department of Endocrinology,Affiliated Hospital of Southwest Medical University,Luzhou 646000,Sichuan Province,China)

机构地区：[1]西南医科大学附属医院眼科,四川省泸州市646000 [2]泸州市第二人民医院眼科,四川省泸州市646100 [3]西南医科大学附属医院内分泌科,四川省泸州市646000

出　　处：《眼科新进展》2021年第1期32-36,共5页Recent Advances in Ophthalmology

基　　金：四川省科学技术厅资助项目(编号2015SZ0086,LZ-LY-37)。

摘　　要：目的研究叔丁基对苯二酚(tBHQ)对2型糖尿病(DM)大鼠视网膜的长期保护作用及其机制。方法将雄性Sprague Dawley大鼠90只随机分为正常对照组(NC组)和造模组。造模组构建2型DM模型,将成模的大鼠进一步随机分为DM组和tBHQ组,tBHQ组于成模后1周在其高脂高糖饲料中加入10 g·L-1 tBHQ进行干预。于tBHQ干预后4周、12周和20周处死各组大鼠,心脏采血检测空腹血糖、低密度脂蛋白(LDL-C)、甘油三脂(TG)和总胆固醇(TC)水平,取大鼠眼球切片行HE染色观察各组大鼠视网膜形态变化,免疫组织化学染色检测各组大鼠视网膜PI3K、缺氧诱导因子1α(HIF-1α)蛋白分布及表达,qRT-PCR检测各组大鼠视网膜中PI3K、HIF-1α及VEGF mRNA的表达。结果干预后4周、12周和20周,3组大鼠间空腹血糖、TC、TG和LDL-C水平差异均具有统计学意义(均为P<0.01);干预后12周和20周,DM组较NC组大鼠空腹血糖、TC、TG、LDL-C水平均升高,tBHQ组较DM组各指标均降低(均为P<0.05)。HE染色结果显示,干预后12周和20周,tBHQ组较DM组视网膜各层排列规则、紧密。免疫组织化学染色检测结果显示,干预后12周、20周,DM组HIF-1α、PI3K蛋白相对表达量均高于同时间点NC组,tBHQ组HIF-1α、PI3K蛋白相对表达量均低于同时间点DM组(均为P<0.05)。qRT-PCR检测结果显示,干预后4周、12周、20周,DM组HIF-1α、VEGF、PI3K mRNA相对表达量均较NC组升高,tBHQ组均较DM组降低,差异均具有统计学意义(均为P<0.05)。结论tBHQ可能通过PI3K/HIF-1α/VEGF信号通路对2型DM大鼠视网膜起长期保护作用。Objective To investigate the long-term protective effect and mechanism of tert-butyl hydroquinone(tBHQ)on the retina of type 2 diabetic rats.Methods Ninety male SD rats were randomly divided into normal group(NC group)and model group.Model group was used to build a type 2 DM model.The modeled rats were further randomly divided into diabetes group(DM group)and tBHQ group.In the tBHQ group,10 g·L-1 tBHQ was added to the high-fat and high-sugar feed one week after forming the model.The rats in each group were sacrificed 4 weeks,12 weeks and 20 weeks after the intervention of tBHQ.Cardiac blood was collected to detect serum fasting blood glucose,low-density lipoprotein(LDL-C),triglyceride(TG)and total cholesterol(TC)levels.Rat eyeball sections were stained with HE to observe the morphological changes of the retina of each group.The distribution and expression of PI3K and hypoxia-inducible factor 1α(HIF-1α)protein in each group were determined by immunohistochemistry,and qRT-PCR was used to determine the expression of PI3K,HIF-1αand VEGF mRNA in the retina of each group.Results At 4 weeks,12 weeks and 20 weeks after the intervention,the differences in fasting blood glucose,TC,TG and LDL-C levels among the three groups of rats were statistically significant(all P<0.01).At 12 weeks and 20 weeks after the intervention,the fasting blood glucose,TC,TG and LDL-C of the DM group were higher than that of the NC group(all P<0.05).The indexes of tBHQ group were lower than those of DM group(all P<0.05).HE staining of retina showed that the cells in the tBHQ group were more regular and tighter than the DM group at 12 and 20 weeks after the intervention.The immunohistochemistry showed that the protein level of retinal HIF-1αand PI3K in the in the DM group was higher than those in the NC group at the same time point at 12 and 20 weeks.HIF-1αand PI3K protein expression levels in the tBHQ group was lower than that in the DM group in the same period(both P<0.05).The qRT-PCR test results at 4 weeks,12 weeks,and 20 weeks after the

关 键 词：叔丁基对苯二酚 糖尿病视网膜病变 PI3K 缺氧诱导因子1Α 2型糖尿病 

分 类 号：R774.1[医药卫生—眼科]