[1]冯闯,左中夫,刘文强,等.抑制JAK/STAT信号通路对糖尿病早期大鼠视网膜Müller细胞的保护作用及对谷氨酸转运蛋白表达的影响[J].眼科新进展,2019,39(2):105-108.[doi:10.13389/j.cnki.rao.2019.0024]
　FENG Chuang,ZUO Zhong-Fu,LIU Wen-Qiang,et al.Inhibition of JAK/STAT signaling pathway protects retinal Müller cells and affects the expression of glutamate transporter in early diabetic rats[J].Recent Advances in Ophthalmology,2019,39(2):105-108.[doi:10.13389/j.cnki.rao.2019.0024]
点击复制

抑制JAK/STAT信号通路对糖尿病早期大鼠视网膜Müller细胞的保护作用及对谷氨酸转运蛋白表达的影响/HTML
分享到：

《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
39卷
期数:
2019年2期
页码:
105-108
栏目:
实验研究
出版日期:
2019-02-05

文章信息/Info

Title:
Inhibition of JAK/STAT signaling pathway protects retinal Müller cells and affects the expression of glutamate transporter in early diabetic rats
作者:
冯闯; 左中夫; 刘文强; 刘学政
110847　辽宁省沈阳市，辽宁中医药大学（冯闯）；121001　辽宁省锦州市，锦州医科大学（左中夫，刘文强，刘学政）
Author(s):
FENG Chuang; ZUO Zhong-Fu; LIU Wen-Qiang; LIU Xue-Zheng
Liaoning University of Traditional Chinese Medicine （FENG Chuang），Shenyang 110847，Liaoning Province，China；Jinzhou Medical University （ZUO Zhong-Fu，LIU Wen-Qiang，LIU Xue-Zheng），Jinzhou 121001，Liaoning Province，China
关键词:
糖尿病视网膜病变; Müller细胞; JAK/STAT信号通路
Keywords:
diabetic retinopathy; Müller cells; JAK/STAT signaling pathway
分类号:
R774
DOI:
10.13389/j.cnki.rao.2019.0024
文献标志码:
A
摘要:
目的　探讨JAK/STAT信号通路对糖尿病早期大鼠视网膜Müller细胞及对谷氨酸转运蛋白（glutamate transporter，GLAST）表达的影响。方法　雄性SD大鼠30只，随机分成对照组、糖尿病组、AG490组，每组10只。后两组大鼠采用单次腹腔注射链脲佐菌素（streptozotocin，STZ） 50 mg·kg-1诱导糖尿病模型。模型诱导成功后，AG490组给予AG490 10 μL（17 mmol·L-1）玻璃体内注射给药。注射1个月后，利用试剂盒检测3组大鼠视网膜中谷氨酸含量变化，免疫荧光检测视网膜GLAST表达，免疫组织化学检测视网膜p-JAK2表达，Western blot检测视网膜GLAST、p-JAK2及p-STAT3蛋白相对表达量。结果　与对照组GLAST相对表达量（65.35±0.66）%、p-JAK2相对表达量（32.80±0.40）%、p-STAT3相对表达量（17.62±1.09）%、谷氨酸含量（23.93±0.67）μmol·g-1相比，糖尿病组视网膜p-JAK2相对表达量（52.16±0.62）%、p-STAT3相对表达量（47.41±0.95）%及谷氨酸含量（44.88±0.27）μmol·g-1均明显增加，GLAST相对表达量（32.96±0.64）%明显下降（均为P<0.01）；而与糖尿病组相比，AG490组p-JAK2相对表达量（13.67±0.45）%、p-STAT3相对表达量（14.47±0.25）%及谷氨酸含量（25.18±0.66） μmol·g-1均明显降低，GLAST相对表达量（49.48±0.32）%明显增加（均为P<0.01）。结论　糖尿病早期大鼠视网膜GLAST表达明显降低，抑制JAK/STAT通路的活化可上调视网膜GLAST表达，降低视网膜谷氨酸含量，这可能有助于减轻糖尿病状态下视网膜Müller细胞的损伤。
Abstract:
Objective　To investigate the effects of JAK/STAT signaling pathway on the expression of glutamate transporter (GLAST) and Müller cells in early diabetic rats.Methods　Thirty clean grade male SD rats were divided into control group,diabetes group and AG490 (JAK2 inhibitor) group according to the random number method,10 rats in each group.The diabetic model was induced by streptozotocin (STZ) (50 mg·kg-1) for the rats in the latter two groups.The AG490 group was given AG490 10μL(17 mM) by intravitreous injection.One month later,the content of glutamate in retina was detected by kits.The expression of GLAST was detected by immunofluorescence.The expression of p-JAK2 was detected by immunohistochemistry.The relative expression of GLAST,p-JAK2 and p-STAT3 was detected by Western blot.Results　Compared with the expression levels of GLAST ［(65.35±0.66)%］,p-JAK2 ［(32.80±0.40)%］,p-STAT3 ［(17.62±1.09)%］ and the content of glutamate ［(23.93±0.67)μmol·g-1］ in control group,the expression levels of p-JAK2 ［(52.16±0.62)%］,p-STAT3 ［(47.41±0.95)%］ and the content of glutamate ［(44.88±0.27)μmol·g-1］ in diabetic group were significantly increased,and the expression level of GLAST ［(32.96±0.64)%］ was significantly decreased (all P<0.01).Compared with diabetes group,the expression levels of p-JAK2 ［(13.67±0.45)%］,p-STAT3 ［(14.47±0.25)%］ and the content of glutamate ［(25.18±0.66) μmol·g-1］ were decreased significantly in AG490 group,and the expression level of GLAST ［(49.48±0.32)%］ was increased significantly (all P<0.01).Conclusion　Inhibition of JAK/STAT pathway activation can up-regulate the expression of GLAST and decrease the content of glutamate in retina,which may help to reduce the damage of retinal Müller cells in diabetic rats.

参考文献/References:

［1］　COUGHLIN B A，FEENSTRA D J，MOHR S.Müller cells and diabetic retinopathy［J］.Vis Res，2017，139：93-100.
［2］　FERNANDEZBUENO I，JONES R，SORIANOROMANí L，LPEZGARCA A，GALVIN O，CHEETHAM S，et al.Histologic characterization of retina neuroglia modifications in diabetic zucker diabetic fatty rats［J］.Invest Ophthalmol Vis Sci，2017，58（11）：4925-4933.
［3］　BOGDANOV P，CORRALIZA L，VILLENA J A，CARVALHO A R，GARCIAARUMí J，RAMOS D，et al.The db/db mouse：a useful model for the study of diabetic retinal neurodegeneration［J］.PLoS One，2014，9（5）：e97302.
［4］　CHEN M，LV H，GAN J，REN J，LIU J.Tang Wang Ming Mu granule attenuates diabetic retinopathy in type 2 diabetes rats［J］.Front Physiol，2017，8：1065.
［5］　VIGNESWARA V，AKPAN N，BERRY M，LOGAN A，TROY C M，AHMED Z.Combined suppression of casp2 and casp6 protects retinal ganglion cells from apoptosis and promotes axon regeneration through cntf-mediated jak/stat signalling［J］.Brain，2014，137（6）：1656-1675.
［6］　ZHANG F J，YI J L，LI J M，LIU Q P.Recent advances in pathological mechanisms of diabetic retinopathy［J］.Rec Adv Ophthalmol，2016，36（6）：584-587.
张凤俊，易敬林，李晶明，刘秋平.糖尿病视网膜病变发病机制研究进展［J］.眼科新进展，2016，36（6）：584-587.
［7］　SOHN E H，VAN DIJK H W，JIAO C，KOK P H，JEONG W，DEMIRKAYA N，et al.Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus［J］.Proc Natl Acad Sci USA，2016，113（19）：2655.
［8］　TIEN T，ZHANG J，MUTO T，KIM D，SARTHY V P，ROY S.High glucose induces mitochondrial dysfunction in retinal müller cells：implications for diabetic retinopathy［J］.Invest Ophthalmol Vis Sci，2017，58（7）：2915-2921.
［9］　ABCOUWER S F.Müller cell-microglia cross talk drives neuroinflammation in diabetic retinopathy［J］.Diabetes，2017，66（2）：261-263.
［10］　DODINGTON D W，DESAI H R，WOO M.Jak/stat - emerging players in metabolism［J］.Trends Endocrin Met，2017，29（1）：55-65.
［11］　SHENG M，HUANG Z，PAN L，YU M，YI C，TENG L，et al.Socs2 exacerbates myocardial injury induced by ischemia/reperfusion in diabetic mice and h9c2 cells through inhibiting the jak-stat-igf-1 pathway［J］.Life Sci，2017，188：101-109.
［12］　LIU M，LI Y，LIANG B，LI Z，JIANG Z，CHU C，et al.Hydrogen sulfide attenuates myocardial fibrosis in diabetic rats through the jak/stat signaling pathway［J］.Int J Mol Med，2018，41（4）：1867-1876.

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]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.
[5]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.
[6]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.
[7]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.
[8]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.
[9]罗文婷 孙大卫.血管黏附蛋白-1在眼科疾病中的研究进展[J].眼科新进展,2013,33(8):000.
[10]李小璐 马雅玲.糖尿病视网膜病变大鼠视网膜VEGF和PEDF的动态表达[J].眼科新进展,2013,33(9):000.
[11]梁汇珉,李赵伟,李铮,等.脑源性神经营养因子对糖尿病大鼠视网膜Müller细胞的保护作用[J].眼科新进展,2017,37(12):1110.[doi:10.13389/j.cnki.rao.2017.0280]
　LIANG Hui-Min,LI Zhao-Wei,LI Zheng,et al.Effect of brain-derived neurotrophic factor on retinal Müller cells in diabetic rats[J].Recent Advances in Ophthalmology,2017,37(2):1110.[doi:10.13389/j.cnki.rao.2017.0280]
[12]李赵伟,梁汇珉,李铮,等.罗格列酮对糖尿病视网膜Müller细胞的保护作用以及对Müller细胞胶质纤维酸性蛋白（GFAP）及炎症因子表达的影响[J].眼科新进展,2018,38(9):825.[doi:10.13389/j.cnki.rao.2018.0195]
　LI Zhao-Wei,LIANG Hui-Min,LI Zheng,et al.The protective effect of rosiglitazone on diabetic retinal Müller cells and its effects on the expression of glial fibrillary acidic protein (GFAP) and inflammatory factors in Müller cells[J].Recent Advances in Ophthalmology,2018,38(2):825.[doi:10.13389/j.cnki.rao.2018.0195]
[13]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]
[14]于洋,刘学政.CDK抑制剂对糖尿病大鼠视网膜Müller细胞胶质增殖及新生血管形成的抑制作用[J].眼科新进展,2019,39(9):809.[doi:10.13389/j.cnki.rao.2019.0184]
　YU Yang,LIU Xue-Zheng.Inhibitory effects of CDK inhibitors on the glial proliferation of retinal Müller cells and retinal neovascularization in diabetic rats[J].Recent Advances in Ophthalmology,2019,39(2):809.[doi:10.13389/j.cnki.rao.2019.0184]
[15]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]
[16]罗影,左中夫,张俏,等.葛花总黄酮对糖尿病视网膜病变大鼠视网膜Müller细胞的保护作用[J].眼科新进展,2020,40(11):1033.[doi:10.13389/j.cnki.rao.2020.0231]
　LUO Ying,ZUO Zhongfu,ZHANG Qiao,et al.Protective effect of total flavonoids of Pueraria on retinal Müller cell in diabetic rats[J].Recent Advances in Ophthalmology,2020,40(2):1033.[doi:10.13389/j.cnki.rao.2020.0231]
[17]王坤,朱曼辉,陈莉莉,等.长链非编码RNA 母系表达基因3调控miR-34a对糖尿病视网膜病变Müller细胞活化及炎症因子分泌的影响[J].眼科新进展,2021,41(1):042.[doi:10.13389/j.cnki.rao.2021.0009]
　WANG Kun,ZHU Manhui,CHEN Lili,et al.Effect of lncRNA MEG3 regulating miR-34a on the activation of Müller cells and the secretion of inflammatory cytokines in diabetic retinopathy[J].Recent Advances in Ophthalmology,2021,41(2):042.[doi:10.13389/j.cnki.rao.2021.0009]
[18]罗影,张俏,单伟.神经胶质成熟因子-β对糖尿病大鼠视网膜Müller细胞活化的影响及可能机制[J].眼科新进展,2023,43(3):190.[doi:10.13389/j.cnki.rao.2023.0038]
　LUO Ying,ZHANG Qiao,SHAN Wei.Effect of glia maturation factor-β on the activation of retinal Müller cells in diabetic rats and its mechanism[J].Recent Advances in Ophthalmology,2023,43(2):190.[doi:10.13389/j.cnki.rao.2023.0038]

备注/Memo

备注/Memo:
国家自然科学基金资助（编号：81571383）；中国博士后科学基金资助（编号：2017M612870）
更新日期/Last Update: 2019-02-18