[1]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):825-828.[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(9):825-828.[doi:10.13389/j.cnki.rao.2018.0195]
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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/HTML
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《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
38卷
期数:
2018年9期
页码:
825-828
栏目:
实验研究
出版日期:
2018-09-05

文章信息/Info

Title:
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
作者:
李赵伟梁汇珉李铮左中夫刘学政
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):
LI Zhao-WeiLIANG Hui-MinLI ZhengZUO Zhong-FuLIU Xue-Zheng
Department of Anatomy,School of Basic Medical Sciences,Jinzhou Medical University,Jinzhou 121001,Liaoning Province,China
关键词:
Müller细胞糖尿病视网膜病变胶质纤维酸性蛋白
Keywords:
müller celldiabetic retinopathyglial fibrillary acidic protein
分类号:
R774
DOI:
10.13389/j.cnki.rao.2018.0195
文献标志码:
A
摘要:
目的 通过建立糖尿病大鼠模型,研究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(glial fibrillary acidic protein,GFAP)及炎症因子表达的影响。方法 取健康清洁级雄性SD大鼠36只,分为对照组、糖尿病组、罗格列酮治疗组,每组12只大鼠。糖尿病组及罗格列酮治疗组大鼠建立糖尿病模型;罗格列酮治疗组每天给予罗格列酮3 mg·kg-1灌胃,糖尿病组和对照组每天给予等体积的生理盐水灌胃。12周后,对大鼠体质量、血糖进行评估。免疫荧光检测大鼠视网膜Müller细胞活化标志物GFAP的表达。利用Western blot对细胞间黏附分子-1(intercellular cell adhesion molecule-1,ICAM-1)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、GFAP的表达变化进行半定量分析。结果 与对照组相比,糖尿病组及罗格列酮治疗组大鼠体质量明显降低,血糖明显升高(均为P<0.01)。与糖尿病组相比,罗格列酮治疗组大鼠体质量无明显变化(P>0.05),但血糖降低(P<0.01)。对照组、糖尿病组、罗格列酮治疗组GFAP免疫荧光表达量分别为82.68±2.65、225.88±5.59、158.89±6.22;与对照组相比,糖尿病组表达量明显增高(P<0.01);与糖尿病组相比,罗格列酮治疗组表达量明显降低(P<0.01)。对照组、糖尿病组、罗格列酮治疗组ICAM-1 蛋白相对表达量分别为(5.91±0.13)%、(57.43±0.92)%、(55.56±1.23)%;与对照组相比,糖尿病组表达量明显增加(P<0.01);与糖尿病组相比,罗格列酮治疗组表达量明显减少(P<0.01)。对照组、糖尿病组、罗格列酮治疗组TNF-α蛋白相对表达量分别为(11.25±1.43)%、(67.36±1.79)%、(44.79±2.12)%;与对照组相比,糖尿病组表达明显增加(P<0.01);与糖尿病组相比,罗格列酮治疗组表达量明显减少(P<0.01)。对照组、糖尿病组、罗格列酮治疗组GFAP蛋白相对表达量分别为(17.79±0.74)%、(64.82±1.23)%、(46.15±2.05)%;与对照组相比,糖尿病组表达明显增加(P<0.01);与糖尿病组相比,罗格列酮治疗组表达量明显减少(P<0.01)。结论 罗格列酮能降低糖尿病视网膜炎症反应,保护Müller细胞,对DR具有潜在的治疗作用。
Abstract:
Objective To investigate the protective effects of rosiglitazone on diabetic retinal Müller cells and its influence on the expression of glial fibrillary acidic protein (GFAP) and inflammatory factors in Müller cells by establishing a rat model of diabetes mellitus.Methods Together 36 male SD rats were divided into three groups in our study and they were control group,diabetic group,rosiglitazone treatment group,with 12 rats in each group.Diabetic model was established in the diabetic group and rosiglitazone treatment group.The rosiglitazone treatment group was given a dose of rosiglitazone 3 mg·kg-1 by gavage everyday.Meanwhile,the diabetic group and the control group were given an equal volume of normal saline.After 12 weeks,we evaluated the rats’ weight and blood glucose concentration and used the immunofluorescence to detect the expression of ICAM-1,TNF-α and GFAP in semi-quantitative analysis by Western blot.Results Compared with the control group,the weight levels of rats in the diabetic group and rosiglitazone treatment group was both obviously decreased (P<0.01),and blood glucose levels were increased (P<0.01).Compared with the diabetic group,the weight of rats in the rosiglitazone treatment group was not obviously decreased (P>0.05).Conversely,blood glucose was reduced.The expression of the quantity of the GFAP by using the immunofluorescence technique was (82.68±2.65) in the control group,(225.88±5.59) in the diabetic group,(158.89±6.22) in the rosiglitazone treatment group.Compared with control group,the expression in the rosiglitazone treatment group was obviously increased (P<0.01),and compared with the diabetic group,the expression in the rosiglitazone treatment group was obviously decreased (P<0.01).The relative expression quantity of ICAM-1 protein in the control group,diabetic group and rosiglitazone treatment group was (5.91±0.13)%,(57.43±0.92)%,and (55.56±1.23)%,respectively.Compared with control group,the expression level in the diabetic group was obviously increased (P<0.01).And compared with the diabetic group,the expression quantity in rosiglitazone treatment group was decreased significantly (P<0.01).The TNF-α protein expression quantity in control group,diabetic group and rosiglitazone treatment group was (11.25±1.43)%,(67.36±1.79)%,(44.79±2.12)%,respectively.Compared with control group,the expression in the diabetic group was obviously increased (P<0.01),and compared with diabetic group,the expression in the rosiglitazone treatment group was decreased significantly (P<0.01).The relative expression quantity of the GFAP protein in the control group,diabetic group and rosiglitazone treatment group was (17.79±0.74)%,(64.82±1.23)%,(46.15±2.05)%,respectively.Compared with control group,the expression levels in the diabetic group was obviously increased (P<0.01),and compared with the diabetic group,the expression quantity in the rosiglitazone treatment group was decreased significantly (P<0.01).Conclusion The rosiglitazone can reduce diabetic retinal inflammatory response and protect Müller cell,which have a potential therapeutic effect on diabetic retinopathy.

参考文献/References:

[1] TUOMILEHTO J,LINDSTRM J,ERIKSSON J G,VALLE T T,HMLINEN H,ILANNEPARIKKA P,et al.Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance[J].N Engl J Med,2001,344(18):1343-1350.
[2] WANG M,MA W,LIAN Z,FARISS R N,WONG W T.Adaptive Müller cell responses to microglial activation mediate neuroprotection and coordinate inflammation in the retina[J].J Neuroinflamm,2011,8(1):173-191.
[3] ZHENG Z,CHEN H,ZHAO H,LIU K,LUO D,CHEN Y,et al.Inhibition of JAK2/STAT3-mediated VEGF upregulation under high glucose conditions by PEDF through a mitochondrial ROS pathway in vitro[J].Invest Ophthalmol Vis Sci,2010,51(1):64-71.
[4] WANG X,LI D,FAN L,XIAO Q,ZUO H,LI Z.CAPE-pNO2 ameliorated diabetic nephropathy through regulating the Akt/NF-κB/iNOS pathway in STZ-induced diabetic mice[J].Oncotarget,2017,8(70):114506-114525.
[5] AHAD A,MUJEEB M,AHSAN H,SIDDIQUI W A.Prophylactic effect of baicalein against renal dysfunction in type 2 diabetic rats[J].Biochimie,2014,106:101-110.
[6] BELLAMY L,CASAS J P,HINGORANI A D,WILLIAMS D.Type 2 diabetes mellitus after gestational diabetes:a systematic review and meta-analysis[J].Lancet,2009,373(9677):1773-1782.
[7] CHAN J C N,MALIK V,JIA W,KADOWAKI T,YAJNIK C S,YOON K H,et al.Diabetes in Asia:Epidemiology,Risk Factors,and Pathophysiology[J].JAMA,2009,301(20):2129-2140.
[8] HARADA T,HARADA C,KOHSAKA S,WADA E,YOSHIDA K,OHNO S,et al.Microglia-müller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration[J].J Neurosci,2002,22(21):9228-9236.
[9] KIDA T,IKEDA T,NISHIMURA M,SUGIYAMA T,IMAMURA Y,SOTOZONO C.Renin-angiotensin system in proliferative diabetic retinopathy and its gene expression in cultured human müller cells[J].Jpn J Ophthalmol,2003,47(1):36-41.
[10] ZUEVA M V,TSAPENKO I V,RIABINA M V,OKHOMTSIMSKAIA T D,GRINCHENKO M I.Changes of retinal neurons and müller glial cells in patients with type II diabetes in treatment of diabetic retinopathy with angiotensin-converting enzyme inhibitor[J].Vestn Oftalmol,2013,129(3):44-51.
[11] CAPOZZI M E,MCCOLLUM G W,COUSINS D B,PENN J S.Linoleic acid is a diabetes-relevant stimulator of retinal inflammation inhuman retinal müller cells and microvascular endothelial cells[J].J Diabetes Metab,2016,7(12):789-792.
[12] VáZQUEZ-CARREA M.Unraveling the effects of ppar-β/δ on insulin resistance and cardiovascular disease[J].Trends Endocrin Met,2016,27(5):319-334.
[13] FISCHER A J,OMAR G,EUBANKS J,MCGUIRE C R,DIERKS B D,REH T A.Different aspects of gliosis in retinal Müller glia can be induced by CNTF,insulin,and FGF2 in the absence of damage[J].Mol Vis,2004,10(115):973-986.
[14] MESHKANI R,SADEGHI A,TAHERIPAK G,ZARGHOONI M,GERAYESH-NEJAD S,BAKHTIYARI S.Rosiglitazone,a PPARγ agonist,ameliorates palmitate-induced insulin resistance and apoptosis in skeletal muscle cells[J].Cell Biochem Funct,2014,32(8):683-691.
[15] LUPIEN C B,SALESSE C.Characterization of two spontaneously generated human muller cell lines from donors with type 1 and type 2 diabetes[J].Invest Ophthalmol Vis Sci,2007,48(2):874-880.
[16] SHELTON M D,DISTLER A M,KERN T S,MIEYAL J J.Glutaredoxin regulates autocrine and paracrine proinflammatory responses in retinal glial (muller) cells[J].J Biol Chem,2009,284(8):4760-4766.
[17] KIM M S,JO H,UM J Y,YI J M,KIM D K,CHOI S C,et al.Agonists of proteinase-activated receptor 2 induce TNF-αsecretion from astrocytoma cells[J].Cell Biochem Funct,2002,20(4):339-345.
[18] WALKER R J,ANDERSON N M,JIANG Y,BAHOUTH S,STEINLE J J.Role of β-adrenergic receptor regulation of tnf-α and insulin signaling in retinal müller cells[J].Invest Ophthalmol Vis Sci,2011,52(13):9527-9533.
[19] YOSHIDA S,YOSHIDA A,ISHIBASHI T.Induction of IL-8,MCP-1,and bFGF by TNF-alpha in retinal glial cells:implications for retinal neovascularization during post-ischemic inflammation[J].Graefes Arch Clin Exp Ophthalmol,2004,242(5):409-422.

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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: 2018-08-31