醛糖还原酶和晚期糖基化终末产物受体对糖尿病视网膜病变神经元凋亡的影响  

Effects of aldose reductase and advanced glycation end products receptor on neuronal apoptosis in diabetic retinopathy

作　　者：董一[1] 万光明[1] 闫磐石[1] 钱诚[1] 梁申芝[1] 王炯[1] DONG Yi;WAN Guang-Ming;YAN Pan-Shi;QIAN Cheng;LIANG Shen-Zhi;WANG Jiong(Department of Ophthalmology,the First Affiliated Hospital of Zhengzhou University (Henan Provincial Eye Hospital),Zhengzhou 450002,Henan Province,China)

机构地区：[1]郑州大学第一附属医院(河南省眼科医院)眼科

出　　处：《眼科新进展》2019年第8期741-745,共5页Recent Advances in Ophthalmology

摘　　要：目的探究醛糖还原酶和晚期糖基化终末产物受体对糖尿病视网膜病变神经元凋亡的影响。方法 Wistar大鼠36只,随机分为对照组、模型组、转染组,后两组建立糖尿病大鼠模型。模型建立成功后,构建含有晚期糖基化终末产物受体siRNA的质粒并利用慢病毒转染入转染组大鼠体内。造模后4周、8周、12周,记录各组大鼠体质量及空腹血糖。造模后9周,禁食6 h,测定口服葡萄糖耐量。造模后12周,处死全部大鼠后,TUNEL法检测各组大鼠视网膜神经元凋亡情况,荧光分光光度计测定醛糖还原酶活性,Western blotting法测定晚期糖基化终末产物受体的表达,RT-PCR检测视网膜中Bcl-2和Bax mRNA相对表达量。结果造模后4周、8周、12周,转染组和模型组的大鼠体质量均低于对照组(均为P<0.05);造模后12周,转染组大鼠体质量高于模型组(P<0.05)。造模后4周、8周、12周,各组内大鼠空腹血糖水平均无明显变化(均为P>0.05),转染组和模型组大鼠的空腹血糖水平均高于对照组(均为P<0.05)。模型组和转染组大鼠在口服葡萄糖后30 min时,血糖水平均高于对照组(均为P<0.05);在120 min时分别下降至最低,但仍高于对照组(均为P<0.05)。模型组和转染组的视网膜神经元凋亡指数、醛糖还原酶活性、晚期糖基化终末产物受体和Bax mRNA相对表达量均高于对照组(均为P<0.05),且转染组均高于模型组(均为P<0.05)。模型组和转染组的Bcl-2 mRNA相对表达量均低于对照组(均为P<0.05),转染组低于模型组(P<0.05)。结论晚期糖基化终末产物结合受体后产生大量的氧自由基损伤,可能是导致糖尿病视网膜神经元凋亡,进而导致糖尿病视网膜病变发生的机制之一。Objective To investigate the effects of aldose reductase and advanced glycation end product receptor on neuronal apoptosis in diabetic retinopathy.Methods Thirty-six Wistar rats were randomly divided into three groups:control group,model group and transfection group,and in the latter two groups,diabetic rat model was established.After successful establishment of the model,the plasmid containing siRNA receptor of advanced glycation end products was constructed and transfected into the transfected rats by lentivirus.At 4 weeks,8 weeks,and 12 weeks after model establishment,the body mass and fasting blood sugar of rats in each group were recorded.Oral glucose tolerance was measured 9 weeks after model establishment and 6 hours after fasting.At 12 weeks after model establishment,all rats were sacrificed.Terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL) method was used to detect the apoptosis of retinal neurons in each group.The activity of aldose reductase was determined by fluorescence spectrophotometer.The receptor for advanced glycation end products was determined by Western blotting.The expression of Bcl-2 and Bax mRNA in the retina was detected by reverse transcription-polymerase chain reaction(RT-PCR).Results At 4 weeks,8 weeks,and 12 weeks after model establishment,the weight of the rats in the transfection group and the model group were lower than those in the control group(all P<0.05).At 12 weeks after model establishment,the weight of the rats in the transfection group were high than those in the model group(P<0.05).At 4 weeks,8 weeks,and 12 weeks after model establishment,there was no significant change in fasting blood glucose levels in the rats in each group(all P>0.05).The fasting blood glucose levels of the transfected group and the model group were higher than those of the control group(all P>0.05).The blood glucose level of the model group and the transfection group was higher than that of the control group 30 min after oral glucose administration(all P<0.05);it decreased to the

关 键 词：糖尿病 视网膜神经元 醛糖还原酶 氧自由基 晚期糖基化终末产物受体 

分 类 号：R774[医药卫生—眼科]