[1]刘文强,王玉波,梁汇珉,等.Nogo蛋白受体(NgR)基因沉默对糖尿病大鼠视网膜神经节细胞密度及突触素表达的影响[J].眼科新进展,2017,37(2):106-109.[doi:10.13389/j.cnki.rao.2017.0028]
 LIU Wen-Qiang,WANG Yu-Bo,LIANG Hui-Min,et al.Effects of inhibiting NgR on retinal ganglion cells density and synaptophysin expression of diabetic rats[J].Recent Advances in Ophthalmology,2017,37(2):106-109.[doi:10.13389/j.cnki.rao.2017.0028]
点击复制

Nogo蛋白受体(NgR)基因沉默对糖尿病大鼠视网膜神经节细胞密度及突触素表达的影响/HTML
分享到:

《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
37卷
期数:
2017年2期
页码:
106-109
栏目:
实验研究
出版日期:
2017-02-05

文章信息/Info

Title:
Effects of inhibiting NgR on retinal ganglion cells density and synaptophysin expression of diabetic rats
作者:
刘文强王玉波梁汇珉李赵伟李铮刘学政
121001 辽宁省锦州市,锦州医科大学基础医学院解剖学教研室
Author(s):
LIU Wen-QiangWANG Yu-BoLIANG Hui-MinLI Zhao-WeiLI ZhengLIU Xue-Zheng
Department of Anatomy,School of Basic Medical Science,Jinzhou Medical University,Jinzhou 121001,Liaoning Province,ChinaResponsible author:LIU Xue-Zheng,E-mail:liuxuezheng168@vip.sina.com;ORCID:0000-0003-2235-4910
关键词:
糖尿病视网膜病变视网膜神经节细胞Nogo蛋白受体突触素
Keywords:
diabetic retinopathyretinal ganglion cellNogo receptorsynaptophysin
分类号:
R774
DOI:
10.13389/j.cnki.rao.2017.0028
文献标志码:
A
摘要:
目的 探讨抑制Nogo蛋白受体(nogo receptor,NgR)对糖尿病大鼠视网膜神经节细胞(retinal ganglion cell,RGC)密度及突触素表达的影响。方法 取雄性SD大鼠32只,随机分成正常对照组、糖尿病组、siNgR组及scNgR组,每组8只。后3组腹腔注射链脲佐菌素(50 mg·kg-1),72 h后尾静脉血糖大于16.7 mmol·L-1的大鼠定为糖尿病模型。siNgR组玻璃体给予腺病毒包装的NgR反义核苷酸序列10 μL,scNgR组玻璃体给予NgR阴性核苷酸序列10 μL,正常对照组及糖尿病组不进行处理。8 周后,HE染色检测RGC密度,免疫荧光技术检测视网膜突触素表达及分布,Western blot检测视网膜NgR及突触素相对表达量。结果 正常对照组、糖尿病组、siNgR组及scNgR组RGC密度分别为(624.33±3.51)个·mm-2、(420.00±2.65) 个·mm-2、(621.67±1.53) 个·mm-2、(416.67±2.52) 个·mm-2。4组间相比,总体差异有统计学意义(F=5985.37,P<0.01)。与正常对照组相比,糖尿病组及scNgR组RGC密度均明显降低(均为P<0.01),而siNgR组无明显变化(P>0.05)。突触素主要表达于视网膜内网层和外网层,与正常对照组相比,糖尿病组及scNgR组阳性表达减少,荧光强度减弱。而siNgR组无明显变化。正常对照组、糖尿病组、siNgR组及scNgR组NgR蛋白相对表达量分别为:(11.26±0.02)%、(19.38±0.10)%、(11.17±0.02)%、(19.47±0.31)%。4组间比较,总体差异有统计学意义(F=2466.09,P<0.01);与正常对照组相比,糖尿病组及scNgR组蛋白相对表达量均增加(均为P<0.01),而siNgR组无明显变化(P>0.05)。突触素蛋白相对表达量分别为:(35.76±0.15)%、(25.47±0.36)%、(35.28±0.12)%、(25.03±0.75)%。4组间比较,总体差异有统计学意义(F=583.70,P<0.01);与正常对照组相比,糖尿病组及scNgR组蛋白相对表达量均降低(均为P<0.01),而siNgR组无明显变化(P>0.05)。结论 抑制糖尿病大鼠视网膜NgR表达有助于恢复突触数量,保护受损的RGC。
Abstract:
Objective To investigate the effects of inhibiting NgR on retinal ganglion cells density and synaptophysin expression of diabetic rat.Methods Thirty-two SD male rats were randomly divided into normal control group,diabetic group,siNgR group and scNgR group,8 rats in each group.Normal control group was given no any treatment.Diabetes model was induced by intraperitoneal injection of 50 mg·kg-1 streptozotocin in diabetic group,siNgR group and scNgR group,and the blood glucose more than 16.7 mmol·L-1 at 72 hours was set as the successfully model.The rats of siNgR group were intravitreally administrated with anti-NgR nucleotide and the rats of scNgR group intravitreally administrated with negative nucleotide.Eight weeks later,HE staining was conducted to detect density of retinal ganglion cell (RGC),immunofluorescence was used to evaluate the expression and distribution of synaptophysin (a marker of synaptic number).Relative expression of NgR and synaptophysin in retina were analyzed by Western blot.Results RGC density in normal control group,diabetes group,siNgR group and scNgR group were (624.33±3.51)mm-2,(420.00±2.65)mm-2,(621.67±1.53)mm-2,(416.67±2.52)mm-2,respectively.There was significant difference among four groups (F=5985.37,P<0.01).Compared with normal control group,RGC density in diabetes group and scNgR group were obviously decreased (all P<0.01),but siNgR group had no obviously change (P>0.05).The synaptophysin mainly expressed in the inner and outer network layer.Compared with normal control group,the positive expression of synaptophysin in diabetes group and scNgR group were decreased,but siNgR group had no obviously change.The relative expression of NgR in normal control group,diabetes group,siNgR group and scNgR group were (11.26±0.02)%,(19.38±0.10)%,(11.17±0.02)%,(19.47±0.31)%,respectively.There was significant difference among four groups (F=2466.09,P<0.01).Compared with normal control group,the relative expression of NgR in diabetes group and scNgR group were obviously decreased (all P<0.01),but siNgR group had no obviously change(P>0.05).The relative expression of synaptophysin in normal control group,diabetes group,siNgR group and scNgR group were (35.76±0.15)%,(25.47±0.36)%,(35.28±0.12)%,(25.03±0.75)%,respectively.There was significant difference among four groups (F=583.70,P<0.01).Compared with the normal control group,the expression of synaptophysin in diabetic group and scNgR group were decreased increased (all P<0.01),while there was no significant difference in siNgR group (P>0.05).Conclusion Inhibiting the expression of NgR in the retina of diabetic rats can help to restore the number of synapses and protect the damaged RGC.

参考文献/References:

[1] JINDAL V.Neurodegeneration as a primary change and role of neuroprotection in diabetic retinopathy [J].Mol Neurobiol,2015,51(3):878-884.
[2] NG DS,CHIANG PP,TAN G,CHEUNG CM,CHENG CY,CHEUNG CY,et al.Retinal ganglion cell neuronal damage in diabetes and diabetic retinopathy[J].Clin Exp Ophthalmol,2016,44(4):243-250.
[3] LIU X,ZUO Z,LIU W,WANG Z,HOU Y,FU Y,et al.Upregulation of nogo receptor expression induces apoptosis of retinal ganglion cells in diabetic rats[J].Neural Regen Res,2014,9(8):815-820.
[4] FU QL,LIAO XX,LI X,CHEN D,SHI J,WEN W,et al.Soluble nogo-66 receptor prevents synaptic dysfunction and rescues retinal ganglion cell loss in chronic glaucoma[J].Invest Ophthalmol Vis Sci,2011,52(11):8374-8380.
[5] 中华医学会糖尿病学分会.中国2型糖尿病防治指南(2013年版) [J].中华内分泌代谢杂志,2014,30(10):26-89.
THE CHINESE DIABETES SOCIETY.The prevention guide of type 2 diabetes in China (2013)[J].Chin J Endocrinol Metab,2014,30(10):26-89.
[6] CHEW EY.There is level 1 evidence for intensive glycemic control for reducing the progression of diabetic retinopathy in persons with type 2 diabetes[J].Endocrine,2015,49(1):1-3.
[7] POURABDOLHOSSEIN F,MOZAFARI S,MORVANDUBOIS G,MIRNAJAFIZADEH J,LOPEZJUAREZ A,PIERRESIMONS J,et al.Nogo receptor inhibition enhances functional recovery following lysolecithin-induced demyelination in mouse optic chiasm[J].PLoS One,2014,9(9):e106378-e106378.
[8] YIN X,ChEN C,YUAN R,YE J.An immunofluorescence-histochemistry study of t21he nogo receptor in the rat retina during postnatal development[J].Ann Ophthalmol,2007,39(2):140-144.
[9] ZHOU L,HUANG J,WANG H,LUO J,ZENG L,XIONG K,et al.Expression of glutamate and gaba during the process of rat retinal synaptic plasticity induced by acute high intraocular pressure[J].Acta Histochem Cytoc,2013,46(1):11-18.
[10] GORDON SL,LEUBE RE,COUSIN MA.Synaptophysin is required for synaptobrevin retrieval during synaptic vesicle endocytosis[J].J Neurosci,2011,31(39):14032-14036.
[11] HUANG J,ZHOU L,HUI W,JIA L,XIONG K,ZENG L,et al.Spatiotemporal alterations of presynaptic elements in the retina after high intraocular pressure[J].Neural Regen Res,2012,7(16):1234-1240.
[12] HELLSTRM M,HARVEY AR.Retinal ganglion cell gene therapy and visual system repair [J].Curr Gene Ther,2011,11(2):116-131.
[13] HELLSTRM M,POLLETT MA,HARVEY AR.Post-injury delivery of rAAV2-CNTF combined with short-term pharmacotherapy is neuroprotective and promotes extensive axonal regeneration after optic nerve trauma [J].J Neurotraum,2011,28(12):2475-2483.

相似文献/References:

[1]杜玮 刘子扬 周艳艳 雒雷鸣.糖尿病视网膜病变与血清胆红素水平的关系[J].眼科新进展,2012,32(5):000.
[2]范松涛 卢建民.阿司匹林与糖尿病患者玻璃体出血以及玻璃体切割术疗效的相关性研究[J].眼科新进展,2012,32(11):000.
[3]李艳 李筱荣 袁佳琴 潘斌.糖尿病大鼠视网膜中VEGF、PEDF的表达与血-视网膜屏障损伤[J].眼科新进展,2013,33(1):000.
[4]喻小龙 谭钢 刘二华 周寿红.罗格列酮对高糖诱导视网膜神经节细胞损伤的保护作用[J].眼科新进展,2013,33(2):000.
[5]李朝晖 崔治华 胡晓英 孟丽珠 张敬维.糖尿病视网膜病变激光面积与疗效的分析[J].眼科新进展,2013,33(2):000.
[6]冯冬梅 朱鸿 施彩虹.CXC趋化因子及其受体在糖尿病视网膜病变中的作用[J].眼科新进展,2013,33(6):000.
[7]牛淑玲.糖尿病视网膜病变患者HbAlc、FPG与血小板参数的变化及危险因素分析[J].眼科新进展,2013,33(7):000.
[8]毕春潮 王睿 王建洲 雷春灵 董晓娟 王小莉 薛晓辉.Ad-PEDF对糖尿病视网膜病变大鼠视网膜新生血管的抑制作用[J].眼科新进展,2013,33(8):000.
[9]梁静 万新顺.川芎嗪对慢性高眼压大鼠视网膜神经节细胞凋亡的影响[J].眼科新进展,2013,33(8):000.
[10]杨萍 孙书明 李晓鹏.辛伐他汀对糖尿病视网膜病变和炎症因子的影响[J].眼科新进展,2013,33(8):000.
[11]马殿伟,谢学军,张梅,等.补肾活血剂对高糖和(或)缺氧状态下视网膜神经节细胞活力及谷氨酰胺合成酶活性的影响[J].眼科新进展,2014,34(6):510.[doi:10.13389/j.cnki.rao.2014.0140]
[12]马殿伟,谢学军,张梅,等. 补肾活血剂对高糖和(或)缺氧状态下共同培养视网膜神经节细胞和Müller细胞谷氨酸代谢的影响[J].眼科新进展,2015,35(5):419.[doi:10.13389/j.cnki.rao.2015.0114]
 MA Dian-Wei,XIE Xue-Jun,ZHANG Mei,et al. Effects of BuShenSuoXue decoction on glutamate metabolism in retinal ganglion cells and Müller cells cocultured in high glucose concentration or ( and) hypoxic conditions[J].Recent Advances in Ophthalmology,2015,35(2):419.[doi:10.13389/j.cnki.rao.2015.0114]
[13]周琼,肖昂. 雷珠单抗对糖尿病大鼠早期视网膜组织结构的影响[J].眼科新进展,2015,35(9):827.[doi:10.13389/j.cnki.rao.2015.0226]
 ZHOU Qiong,XIAO Ang. Effects of ranibizumab on retinal structure at early stage of diabetic rats[J].Recent Advances in Ophthalmology,2015,35(2):827.[doi:10.13389/j.cnki.rao.2015.0226]
[14]沈沛阳,陈王灵,冼文光,等.采用频域OCT观察糖尿病患者早期黄斑区视网膜结构的变化[J].眼科新进展,2017,37(1):042.[doi:10.13389/j.cnki.rao.2017.0011]
 SHEN Pei-Yang,CHEN Wang-Ling,XIAN Wen-Guang,et al.Evaluation of early diabetic macular morphology changes using SD-OCT[J].Recent Advances in Ophthalmology,2017,37(2):042.[doi:10.13389/j.cnki.rao.2017.0011]
[15]钱道卫,廖燕秋,李远存,等.沉默信息调节因子相关酶1(SIRT1)调控p38MARK信号通路对糖尿病视网膜病变大鼠视网膜神经节细胞的保护作用及机制[J].眼科新进展,2017,37(10):926.[doi:10.13389/j.cnki.rao.2017.0235]
 QIAN Dao-Wei,LIAO Yan-Qiu,LI Yuan-Cun,et al.Protective effects and mechanism of SIRT1 for the regulation of p38 MAPK pathway on retinal ganglion cells in rats with diabetic retinopathy[J].Recent Advances in Ophthalmology,2017,37(2):926.[doi:10.13389/j.cnki.rao.2017.0235]
[16]张俏,刘文强,左中夫,等.褪黑素通过Müller细胞保护糖尿病视网膜神经节细胞的机制[J].眼科新进展,2019,39(7):611.[doi:10.13389/j.cnki.rao.2019.0141]
 ZHANG Qiao,LIU Wen-Qiang,ZUO Zhong-Fu,et al.Protective effects of melatonin on diabetic retinal ganglion cell via Müller cell[J].Recent Advances in Ophthalmology,2019,39(2):611.[doi:10.13389/j.cnki.rao.2019.0141]
[17]王英,吴会平,王冬冬,等.重组碱性成纤维细胞生长因子通过Notch1信号通路对糖尿病大鼠视网膜神经节细胞的保护作用[J].眼科新进展,2019,39(10):911.[doi:10.13389/j.cnki.rao.2019.0207]
 WANG Ying,WU Hui-Ping,WANG Dong-Dong,et al.Protective effect of recombinant basic fibroblast growth factor on retinal ganglion cells via Notch1 signaling pathway in diabetic rats[J].Recent Advances in Ophthalmology,2019,39(2):911.[doi:10.13389/j.cnki.rao.2019.0207]
[18]吴传玲,刘安琪,左中夫,等.Raf-1激酶抑制蛋白(RKIP)对糖尿病大鼠视网膜神经损伤的保护作用[J].眼科新进展,2020,40(4):323.[doi:10.13389/j.cnki.rao.2020.0074]
 WU Chuanling,LIU Anqi,ZUO Zhongfu,et al.Protective effect of RKIP on retinal nerve injury in diabetic rats through p38-MAPK pathway[J].Recent Advances in Ophthalmology,2020,40(2):323.[doi:10.13389/j.cnki.rao.2020.0074]
[19]皮百木,宋玫侠.PACAP38调控TRPC6表达对糖尿病视网膜病变大鼠的保护作用[J].眼科新进展,2020,40(7):625.[doi:10.13389/j.cnki.rao.2020.0143]
 PI Baimu,SONG Meixia.Regulation effect of PACAP38 on TRPC6 expression in diabetic retinopathy rats[J].Recent Advances in Ophthalmology,2020,40(2):625.[doi:10.13389/j.cnki.rao.2020.0143]
[20]于洋,刘学政.GPR120通过抑制核因子-κB信号通路对糖尿病大鼠视网膜神经节细胞损伤的保护作用[J].眼科新进展,2021,41(10):905.[doi:10.13389/j.cnki.rao.2021.0190]
 YU Yang,LIU Xuezheng.Protective effect of GPR120 on injured retinal ganglion cells in diabetic rats by inhibiting nuclear factor-κB signaling pathway[J].Recent Advances in Ophthalmology,2021,41(2):905.[doi:10.13389/j.cnki.rao.2021.0190]

备注/Memo

备注/Memo:
 国家自然科学基金资助(编号:81571383)
更新日期/Last Update: 2017-03-01