[1]董一,万光明,闫磐石,等.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[J].眼科新进展,2019,39(8):741-745.[doi:10.13389/j.cnki.rao.2019.0169]
　DONG Yi,WAN Guang-Ming,YAN Pan-Shi,et al.Effects of aldose reductase and advanced glycation end products receptor on neuronal apoptosis in diabetic retinopathy[J].Recent Advances in Ophthalmology,2019,39(8):741-745.[doi:10.13389/j.cnki.rao.2019.0169]
点击复制

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/HTML
分享到：

《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
39卷
期数:
2019年8期
页码:
741-745
栏目:
实验研究
出版日期:
2019-08-05

文章信息/Info

Title:
Effects of aldose reductase and advanced glycation end products receptor on neuronal apoptosis in diabetic retinopathy
作者:
董一; 万光明; 闫磐石; 钱诚; 梁申芝; 王炯
450002　河南省郑州市，郑州大学第一附属医院（河南省眼科医院）眼科
Author(s):
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
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
Keywords:
diabetes; retinal neurons; aldose reductase; oxygen free radicals; advanced glycation end product receptors
分类号:
R774
DOI:
10.13389/j.cnki.rao.2019.0169
文献标志码:
A
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。
Abstract:
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 lowest at 120 min,but still higher than the control group (all P>0.05).The retinal neuron apoptosis index,aldose reductase activity,advanced glycation end product receptor and Bax mRNA expression in the model group and the transfected group were higher than those in the control group (all P>0.05).The staining group was higher than the model group (all P>0.05).The relative expression of Bcl-2 mRNA in the model group and the transfected group was lower than that in the control group (all P>0.05),and the transfection group was lower than the model group (P>0.05).Conclusion　After the late glycation end products bind to the receptor,the production of a large number of oxygen free radical damage may be one of the mechanisms leading to the apoptosis of diabetic retinal neurons,which leads to the development of diabetic retinopathy.

参考文献/References:

［1］　STITT A W，CURTIS T M，CHEN M，MEDINA R J，MCKAY G J，JENKINS A，et al.The progress in understanding and treatment of diabetic retinopathy［J］.Prog Retin Eye Res，2016，51（3）：156-186.
［2］　KAWASAKI R，KITANO S，SATO Y，YAMASHITA H，NISHIMURA R，TAJIMA N，et al.Factors associated with non-proliferative diabetic retinopathy in patients with type 1 and type 2 diabetes：the Japan Diabetes Complication and its Prevention prospective study （JDCP study 4）［J］.Diabetol Int，2016，10（1）：3-11.
［3］　GOK M，ALTAS H，KAPTI H B.The impact of intravitreal dexamethasone implant on retrobulbar hemodynamics in patients with diabetic macular edema and retinal vein occlusions［J］.Cutan Ocul Toxicol，2019，17（2）：1-23.
［4］　WANG X J，LIU C S，LI Z X，SUN L P，LIU L，HAI X，et al.The effect of baicalin on tissue aldose reductase activity and retinal apoptosis in diabetic rats［J］.Chin J Diabetes，2008，16（8）：507-508.
王秀军，刘长山，李兆欣，孙丽萍，柳林，海霞，等.黄芩苷对糖尿病大鼠组织醛糖还原酶活性及视网膜细胞凋亡的影响［J］.中国糖尿病杂志，2008，16（8）：507-508.
［5］　TING D S，CHEUNG G C，WONG T Y.Global prevalence and major risk factors of diabetic retinopathy［J］.Diabetes Care，2016，35（3）：556-564.
［6］　CHEN X.Anti-apoptosis of neurons in diabetic retinopathy in animals with compound xueshuantong［D］.Guangzhou:Sun Yat-sen University，2007.
陈潇.复方血栓通抗糖尿病视网膜病变神经元凋亡的动物研究［D］.广州：中山大学，2007.
［7］　OLA M S，AL-DOSARI D，ALHOMIDA A S.Role of oxidative stress in diabetic retinopathy and the beneficial effects of flavonoids［J］.Curr Pharm Des，2013，8（6）：808-810.
［8］　ADAMSKA A，ARASZKIEWICZ A，PILACINSKI S，GANDECKA A，GRZELKA A，KOWALSKA K，et al.Dermal microvessel density and maturity is closely associated with atherogenic dyslipidemia and accumulation of advanced glycation end products in adult patients with type 1 diabetes［J］.Microvasc Res，2019，121（1）：46-51.
［9］　WANG K J，ZHAO J L.Corn silk （Zea mays L.），a source of natural antioxidants with α-amylase，α-glucosidase，advanced glycation and diabetic nephropathy inhibitory activities［J］.Biomed Pharmacother，2019，110（2）：510-517.
［10］　WANG K，LV H B，DAI Y，ZHAO Y.Study on the association between diabetic retinopathy neuronal apoptosis and gene polymorphisms of AGEs receptor［J］.J Southeast Univ （Med Sci Edit），2017，36（6）：954-957.
王科，吕红彬，代艳，赵媛.糖尿病视网膜病变神经元凋亡与晚期糖基化终产物受体基因多态性的相关性研究［J］.东南大学学报：医学版，2017，36（6）：954-957.
［11］　PAN Y，DUAN W，ZENG X Q，ZHANG Z Y.Relationship between Bcl-2/Bax and vascular calcification in rat aorta［J］.Xinxiang Med Univ，2015，32（3）：213-215，219.
潘莹，段雯，曾宪钦，张志远.Bcl-2/Bax与大鼠主动脉钙化的关系［J］.新乡医学院学报，2015，32（3）：213-215，219.
［12］　SONG X Y，CHEN Q，QI X Y.Effect of liuwei dihuang pill on erythrocyte aldose reductase activity in early diabetic nephropathy patients［J］.Chin J Int Trad Western Med，2004，24（12）：1087-1090.
宋晓燕，陈蔷，齐晓燕.六味地黄丸对早期糖尿病肾病患者红细胞醛糖还原酶活性的影响［J］.中国中西医结合杂志，2004，24（12）：1087-1090.
［13］　JAISWAL S，MISHRA S，TORGAL S S，SHENGULE S.Neuroprotective effect of epalrestat mediated through oxidative stress markers，cytokines and TAU protein levels in diabetic rats［J］.Life Sci，2018，207（8）：364-371.
［14］　ROWAN S，BEJARANO E，TAYLOR A.Mechanistic targeting of advanced glycation end-products in age-related diseases［J］.Biochim Biophys Acta Mol Basis Dis，2018，1864（12）：3631-3643.
［15］　XU J，CHEN L J，YU J，WANG H J，ZHANG F，LIU Q，et al.Involvement of advanced glycation end products in the pathogenesis of diabetic retinopathy［J］.Cell Physiol Biochem，2018，48（2）：705-717.
［16］　LOHO T，VENNA V，SETIABUDY R D，SUKARTINI N，IMMANUEL S，KUMALAWATI J，et al.Correlation between vitreous advanced glycation end products，and D-dimer with blood HbA1c levels in proliferative diabetic retinopathy［J］.Acta Med Indones，2018，50（2）：132-137.
［17］　KAHYA M C，NAZIRO G · LU M，VEY I · S.Modulation of diabetes-induced oxidative stress，apoptosis，and Ca2+ entry through TRPM2 and TRPV1 channels in dorsal root ganglion and hippocampus of diabetic rats by melatonin and selenium［J］.Mol Neurobiol，2017，54（3）：2345-2360.
［18］　PEKTA M B，SADI G，KOCA H B，YUKSEL Y，VURMAZ A，KOCA T，et al.Resveratrol ameliorates the components of hepatic inflammation and apoptosis in a rat model of streptozotocin-induced diabetes［J］.Drug Dev Res，2016，77（1）：12-19.

相似文献/References:

[1]丁文君 韦琦 梁皓 陈金卯 李霞 谭少健.糖尿病兔后发性白内障发生过程中晶状体上皮细胞增殖的变化[J].眼科新进展,2012,32(1):000.
[2]陈放 徐珊 吕伟红 程宏 张洪泉.糖尿病大鼠视网膜的氧化应激损伤及葛根素对其的干预作用[J].眼科新进展,2012,32(1):000.
[3]李晓艳 张卯年.褪黑素对糖尿病大鼠早期视网膜神经细胞凋亡的影响[J].眼科新进展,2012,32(6):000.
[4]楚静 陈忠平.普拉洛芬及羟苯磺酸钙在糖尿病患者白内障手术中的应用[J].眼科新进展,2013,33(8):000.
[5]张曙光 何跃 项杰 马林昆 李燕 袁援生.JNK2在早期糖尿病小鼠视网膜中的表达及作用[J].眼科新进展,2012,32(4):000.
[6]李艳 潘斌 李筱荣 袁佳琴 张杰.糖尿病大鼠视网膜PEDF表达与神经退行性改变[J].眼科新进展,2012,32(8):000.
[7]崔颖 郭海科 韩云飞 孟倩丽 张良 尹东明.2型糖尿病住院患者糖尿病视网膜病变患病率及危险因素分析[J].眼科新进展,2012,32(8):000.
[8]张谊 宋光辉 杨架林 张钰 肖强 潘璐 赵伟红 刘昊.糖尿病患者短期内血糖变化对黄斑区视网膜厚度的影响[J].眼科新进展,2012,32(10):000.
[9]赵恳.白内障超声乳化人工晶状体植入术对糖尿病患者角膜内皮细胞形态与功能的影响[J].眼科新进展,2013,33(4):000.
[10]张立新 崔颖 孟倩丽 张敏 罗中伶 刘辉焜 朱国平 香淦媚 刘清洋 郭海科 郑洋 蔡晶晶. 广东省东莞市2型糖尿病患者盲与低视力患病率及原因分析[J].眼科新进展,2014,34(1):046.

更新日期/Last Update: 2019-07-31