[1]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):911-915.[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(10):911-915.[doi:10.13389/j.cnki.rao.2019.0207]
点击复制

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/HTML
分享到：

《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
39卷
期数:
2019年10期
页码:
911-915
栏目:
实验研究
出版日期:
2019-10-05

文章信息/Info

Title:
Protective effect of recombinant basic fibroblast growth factor on retinal ganglion cells via Notch1 signaling pathway in diabetic rats
作者:
王英; 吴会平; 王冬冬; 刘学政
121001　辽宁省锦州市，锦州医科大学解剖学教研究(王英，刘学政)；121001　辽宁省锦州市，锦州医科大学附属第一医院(吴会平，王冬冬)
Author(s):
WANG Ying; WU Hui-Ping; WANG Dong-Dong; LIU Xue-Zheng
Department of Anatomy,Jinzhou Medical University (WANG Ying,LIU Xue-Zheng),the First Affiliated Hospital of Jinzhou Medical University (WU Hui-Ping,WANG Dong-Dong),Jinzhou 121001,Liaoning Province,China
关键词:
糖尿病视网膜病变; 视网膜神经节细胞; 重组碱性成纤维细胞生长因子; Notch1信号通路; 生长相关蛋白-43
Keywords:
diabetic retinopathy; retinal ganglion cell; recombinant basic fibroblast growth factor; Notch1 signal pathway; growth associated protein-43
分类号:
R774.1
DOI:
10.13389/j.cnki.rao.2019.0207
文献标志码:
A
摘要:
目的　探讨重组碱性成纤维细胞生长因子(recombinant basic fibroblast growth factor,rbFGF)通过Notch1信号通路对糖尿病大鼠视网膜神经节细胞(retinal ganglion cell，RGC)的保护作用。方法　雄性SD大鼠40只，随机分成对照组、糖尿病组、rbFGF组、rbFGF+DAPT组(DAPT为Notch1通路的特异性拮抗剂)，每组10只。后三组大鼠采用单次腹腔注射链脲佐菌素(streptozotocin,STZ) 诱导糖尿病模型。模型诱导成功后，rbFGF组给予rbFGF 10 μL(200 U)玻璃体内注射给药，rbFGF+DAPT组在给予rbFGF基础上加用DAPT(10 μmol·L-1)。注射12周后，HE染色检测RGC密度，免疫组织化学染色检测神经元再生相关蛋白GAP-43、Notch1蛋白表达，Western blot检测GAP-43、Notch1蛋白及凋亡相关蛋白Caspase-3相对表达量。结果　与对照组RGC密度(433.49±6.02)个·mm-2，GAP-43荧光强度(8.96±0.26)%、Notch1阳性率(45.04±0.46)%及Caspase-3 (27.91±0.63) %蛋白表达相比，糖尿病组RGC密度(328.35±6.43)mm-2，Notch1荧光强度(31.66±0.40)%蛋白表达明显降低，GAP-43荧光强度(13.66±0.52)%、Caspase-3 (48.91±0.64)%蛋白表达明显增加(均为P<0.05)；而与糖尿病组相比，rbFGF组RGC密度(425.30±7.98)个·mm-2，Notch1阳性率(41.76±0.62)% 及GAP-43荧光强度(33.05±0.37)%蛋白表达明显增加，Caspase-3 (28.86±0.71)%蛋白表达明显降低(均为P<0.05)；而rbFGF+DAPT组RGC密度(324.91±8.22)个·mm-2，GAP-43荧光强度(14.27±0.64)%、Notch1阳性率(30.40±0.82)%及Caspase-3 (47.63±0.68)%蛋白表达均无明显变化(均为P>0.05)。结论　rbFGF可上调糖尿病状态下视网膜GAP-43蛋白表达，下调Caspase-3蛋白表达，进而提高RGC的存活，其机制可能与激活Notch1信号通路有关。
Abstract:
Objective　To investigate the protective effect of recombinant basic fibroblast growth factor (rbFGF) on retinal ganglion cell (RGC) in diabetic rats via Notch1 signaling pathway.Methods　Totally 40 male SD rats were randomly divided into control group,diabetic group,rbFGF group,rbFGF+DAPT group (DAPT is a specific antagonist of Notch1 pathway),10 rats in each group.The diabetic rats in the latter three groups were induced by single intraperitoneal (IP) injection of streptozotocin (STZ).After successful induction of the model,rbFGF group was given intravitreal injection of rbFGF 10 μL (200 U),while rbFGF+DAPT group was given rbFGF 10 μL and DAPT (10 μmol·L-1).After 12 weeks of injection,the density of RGC was detected by HE staining,the protein expression of growth associated protein-43(GAP-43) and Notch1 was detected by immunohistochemical staining,and relative protein expression of GAP-43,Notch1 and Caspase-3 was detected by Western blot.Results　Compared with the density of RGC ［(433.49±6.02)cells·mm-2］ and fluorescence intensity of GAP-43 ［(8.96±0.26)%］,positive rate of Notch1 ［(45.04±0.46)%］,the protein expression of Caspase-3［(27.91±0.63)%］ in the control group,the density of RGC ［(328.35±6.43)cells·mm-2］ and fluorescence intensity of Notch1 ［(31.66±0.40)%］ were decreased significantly,while the fluorescence intensity of GAP-43 ［(13.66±0.52)%］,the protein expression of Caspase-3 ［(48.91±0.64)%］ in diabetic group were increased significantly (all P<0.05).Compared with the diabetic group,the density of RGC ［(425.30±7.98)cells·mm-2］ and the fluorescence intensity of GAP-43 ［(33.05±0.37)%］,positive rate of Notch1［(41.76±0.62)%］ were increased significantly,while the protein expression of Caspase-3 ［(28.86±0.71)%］ in rbFGF group was decreased significantly (all P<0.05);but the density of RGC ［(324.91±8.22)cells·mm-2］,the fluorescence intensity of GAP-43 ［(14.27±0.64)%］,positive rate of Notch1［(30.40±0.82)%］ and the protein expression of Caspase-3［(47.63±0.68)%］ in rbFGF+DAPT group were no significantly change (all P>0.05).Conclusion　RbFGF can up-regulate the protein expression of GAP-43 and down-regulate the protein expression of Caspase-3 in the retina of diabetes rats,thus improving the survival of RGC.The mechanism may be related to activation of Notch1 signaling pathway.

参考文献/References:

［1］　KARTI O，NALBANTOGLU O，ABALI S，AYHAN Z，TUNC S，KUSBECI T，et al.Retinal ganglion cell loss in children with type 1 diabetes mellitus without diabetic retinopathy［J］.Ophthalmic Surg Lasers Imaging Retina,2017,48(6):473-477.
［2］　HAIYAN J,JINLIN D,JUAN S,YANQI L,MENGJUAN W,JING Z,et al.Loss-of-function mutation of serine racemase attenuates retinal ganglion cell loss in diabetic mice［J］.Exp Eye Res,2018,175(10):90-97.
［3］　MADDALUNO L,URWYLER C,WERNER S.Fibroblast growth factors:key players in regeneration and tissue repair［J］.Development,2017,144(22):4047-4060.
［4］　YANG H T,YAO P,BAO Y X.Protective effects of ciliary neurotrophic factor and basic fibroblast growth factor on optic nerve injury［J］.Chin J Pharm Econ,2013，14(3):263-264.
杨惠婷,姚鹏,鲍永新.睫状神经营养因子和碱性成纤维细胞生长因子对视神经损伤保护的研究［J］.中国药物经济学,2013，14(3):263-264.
［5］　JIAN Q,TAO Z,LI Y,YIN Z Q.Acute retinal injury and the relationship between nerve growth factor,Notch1 transcription and short-lived dedifferentiation transient changes of mammalian müller cells［J］.Vision Res,2015,110(5):107-117.
［6］　LI X,HU A L,ZHENG Y Y,XU H,TAO C C.Effect of recombinant basic fibroblast growth factor on rat retinal ganglion cells［J］.Chin J Pathophy,2002,18(2):147-149.
［7］　LI L,CHEN L P,LIU Q H.Effect of the Notch signaling pathway on retinal ganglion cells and its neuroprotection in rats with acute ocular hypertension［J］.Int J Ophthalmol,2018,11(2):208-215.
［8］　MUC R,SARACEN A,GRABSKA-LIBEREK I.Associations of diabetic retinopathy with retinal neurodegeneration on the background of diabetes mellitus.Overview of recent medical studies with an assessment of the impact on healthcare systems［J］.Open Med,2018，13(1):130-136.
［9］　LI Z,LIANG H M,LI Z W,LIU X Z.Role of nerve growth factor in synaptic plasticity of retina in diabetic rats［J］.Rec Adv Ophthalmol,2017,37(9):816-818.
李铮,梁汇珉,李赵伟,刘学政.神经生长因子在糖尿病大鼠视网膜突触可塑性中的作用［J］.眼科新进展,2017,37(9):816-818.
［10］　LI P,XU X,ZHENG Z,ZHU B,SHI Y,LIU K.Protective effects of rosiglitazone on retinal neuronal damage in diabetic rats［J］.Curr Eye Res,2011,36(7):673-679.
［11］　GUO X,LIU X.Nogo receptor knockdown and ciliary neurotrophic factor attenuate diabetic retinopathy in streptozotocin-induced diabetic rats［J］.Mol Med Rep,2017,16(2):2030-2036.
［12］　LI P,XU X,ZHENG Z,ZHU B,SHI Y,LIU K.Curcumin improves neural function after spinal cord injury by the joint inhibition of the intracellular and extracellular components of glial scar［J］.J Surg Res,2015,195(1):235-245.
［13］　MOHAMED R,ELREMESSY A B.Imbalance of the nerve growth factor and its precursor:implication in diabetic retinopathy［J］.J Clin Exp Ophthalmol,2015,6(5):483.
［14］　ITO M.Insulin or bFGF and C2 ceramide increase newborn rat retinal ganglion cell survival rate［J］.Biochem Biophys Res Commun,2003,301(2):564-571.
［15］　ALTMANN C,VASIC V,HARDT S,HEIDLER J,HUSSLER A,WITTIG I,et al.Progranulin promotes peripheral nerve regeneration and reinnervation:role of notch signaling［J］.Mol Neurodegener,2016,11(1):69-91.

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(10):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(10):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(10):042.[doi:10.13389/j.cnki.rao.2017.0011]
[15]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.[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(10):106.[doi:10.13389/j.cnki.rao.2017.0028]
[16]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(10):926.[doi:10.13389/j.cnki.rao.2017.0235]
[17]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(10):611.[doi:10.13389/j.cnki.rao.2019.0141]
[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(10):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(10):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(10):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: 2019-10-12