[1]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):905-909.[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):905-909.[doi:10.13389/j.cnki.rao.2021.0190]
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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/HTML
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《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
41卷
期数:
2021年10期
页码:
905-909
栏目:
实验研究
出版日期:
2021-10-05

文章信息/Info

Title:
Protective effect of GPR120 on injured retinal ganglion cells in diabetic rats by inhibiting nuclear factor-κB signaling pathway
作者:
于洋刘学政
121001 辽宁省锦州市,锦州医科大学附属第一医院(于洋);121001 辽宁省锦州市,锦州医科大学解剖学教研室 (刘学政)
Author(s):
YU Yang1LIU Xuezheng2
1.The First Affiliated Hospital of Jinzhou Medical University,Jinzhou 121001,Liaoning Province,China
2.Department of Anatomy,Jinzhou Medical University,Jinzhou 121001,Liaoning Province,China
关键词:
糖尿病视网膜病变视网膜神经节细胞GPR120核因子-κB神经损伤
Keywords:
diabetic retinopathy retinal ganglion cells GPR120 nuclear factor-κB nerve injury
分类号:
R774.1
DOI:
10.13389/j.cnki.rao.2021.0190
文献标志码:
A
摘要:
目的 探讨GPR120对糖尿病大鼠视网膜神经节细胞(RGC)的影响及可能机制。方法 健康雄性SD大鼠按55 mg·kg-1腹腔一次性注射链脲佐菌素建立糖尿病大鼠模型。模型诱导成功后,将大鼠随机分成三组:糖尿病组、鱼油预处理组(鱼油1 g·kg-1每天1次灌胃;鱼油的主要成分为omega-3,omega-3为GPR120通路激活剂)、安慰剂组(玉米油1 g·kg-1每天1次灌胃),每组15只,另取15只正常大鼠作为对照组(对照组和糖尿病组大鼠每天1次灌胃等剂量PBS缓冲液)。12周后,气相色谱法检测各组大鼠视网膜组织中二十二碳六烯酸(DHA)和二十碳五烯酸(EPA)含量,HE染色检测RGC密度,免疫荧光染色检测视网膜GPR120蛋白表达,Western blot检测视网膜GPR120、核因子-κB(NF-κB)、半胱氨酸蛋白酶3(Caspase-3)蛋白相对表达量。结果 与对照组相比,糖尿病组大鼠视网膜组织中DHA、EPA含量均明显减少(均为P<0.01);与糖尿病组相比,鱼油预处理组大鼠视网膜组织中DHA、EPA含量均明显增加(均为P<0.01)。GPR120主要分布于RGC层。对照组大鼠RGC密度为(437.06±4.72) 个·mm-2,GPR120、NF-κB、Caspase-3蛋白相对表达量分别为(35.65±0.89)%、(12.42±0.58)%、(13.76±0.08)%;糖尿病组大鼠RGC密度为 (329.75±3.51) 个·mm-2,GPR120、NF-κB、Caspase-3 蛋白相对表达量分别为(24.14±0.46)%、(38.94±0.45)%、(25.14±0.45)%;鱼油预处理组大鼠RGC密度为(412.44±3.62) 个·mm-2,GPR120、NF-κB、Caspase-3蛋白相对表达量分别为(31.59±0.77)%、(18.11±0.58)%、(20.14±0.61)%。与对照组相比,糖尿病组大鼠视网膜NF-κB、Caspase-3蛋白相对表达量均明显增加,RGC密度、GPR120蛋白相对表达量均明显降低;与糖尿病组相比,鱼油预处理组大鼠视网膜NF-κB、Caspase-3蛋白相对表达量均明显降低,RGC密度、GPR120蛋白相对表达量均明显增加(均为P<0.01)。糖尿病组与安慰剂组相比,各指标差异均无统计学意义(均为P>0.05)。结论 GPR120激活对糖尿病大鼠RGC损伤具有保护作用,其机制可能与抑制NF-κB通路有关。
Abstract:
Objective To investigate the effect and possible mechanism of GPR120 on retinal ganglion cells (RGC) in diabetic rats.Methods Healthy male SD rats were given a one-time intraperitoneal injection of streptozotocin (STZ) at 55 mg·kg-1 to make a diabetic rat model. After the model was successfully induced, the rats were randomly divided into three groups: diabetes group, fish oil pretreatment group (gavage dose was 1 g·kg-1 q.i.d, the main ingredient of fish oil was omega-3, which is the GPR120 pathway activator), placebo group (corn oil 1 g·kg-1, q.i.d), 15 rats in each group, and 15 normal rats were taken as the control group (PBS was given to rats in control group and diabetes group with equal dose, q.i.d). After 12 weeks, the content of DHA and EPA in retinal tissue was analyzed by gas chromatography, RGC density was detected by HE staining, GPR120 protein expression in retina was detected by immunofluorescence staining, and the relative protein expression levels of GPR120, nuclear factor-κB (NF-κB), and Caspase-3 were detected by Western blot.Results Compared with the control group, the DHA and EPA in the retinal tissue of rats in diabetes group were significantly decreased (both P<0.01); compared with the diabetes group, the DHA and EPA in the retinal tissue of rats in fish oil pretreatment group were significantly increased (both P<0.01). The GPR120 was mainly distributed in RGC layer. The RGC density in the control group was (437.06±4.72) cells·mm-2, and the relative expression levels of GPR120, NF-κB, and Caspase-3 were respectively (35.65±0.89)%, (12.42±0.58)%, and (13.76±0.08)%; the RGC density in the diabetes group was (329.75±3.51) cells·mm-2, the relative expression levels of GPR120, NF-κB, and Caspase-3 were respectively (24.14±0.46)%, (38.94±0.45)%, and (25.14±0.45)%; the RGC density in fish oil pretreatment group was (412.44±3.62) cells·mm-2, the relative expression levels of GPR120, NF-κB and Caspase-3 were respectively (31.59±0.77)%, (18.11±0.58)%, and (20.14±0.61)%. Compared with the control group, the relative expression levels of NF-κB, and Caspase-3 in the diabetes group were significantly increased, the RGC density and the expression of GPR120 were significantly reduced; compared with the diabetes group, the relative expression levels of NF-κB, and Caspase-3 in the fish oil pretreatment group were significantly reduced, RGC density and the expression of GPR120 were significantly increased (all P<0.01). There was no statistical significance in the variation of indexes between the diabetes group and the placebo group (all P>0.05).Conclusion GPR120 activation has a protective effect on injured RGC in diabetic rats, and its mechanism may be related to the inhibition of NF-κB pathway.

参考文献/References:

[1] ZHOU H R,MA X F,LIN W J,HAO M,YU X Y,LI H X,et al.Neuroprotective role of GLP-1 analog for retinal ganglion cells via PINK1/parkin-mediated mitophagy in diabetic retinopathy[J].Front Pharmacol,2021,11:589114.
[2] ZHANG J,CUI C,XU H.Downregulation of miR-145-5p elevates retinal ganglion cell survival to delay diabetic retinopathy progress by targeting FGF5[J].Biosci Biotechnol Biochem,2019,83(9):1655-1662.
[3] CHENG H H,YE H,PENG R P,DENG J,DING Y.Inhibition of retinal ganglion cell apoptosis:regulation of mitochondrial function by PACAP[J].Neural Regen Res,2018,13(5):923-929.
[4] HU J,XUE P,MAO X,XIE L,LI G,YOU Z.SUMO1/UBC9-decreased Nox1 activity inhibits reactive oxygen species generation and apoptosis in diabetic retinopathy[J].Mol Med Rep,2018,17(1):1690-1698.
[5] CHINTHAKUNTA N,CHEEMANAPALLI S,CHINTHAKUNTA S,ANURADHA C M,CHITTA S K.A new insight into identification of in silico analysis of natural compounds targeting GPR120[J].Netw Model Anal Health Inform Bioinform,2018,7(1):8-10.
[6] YIN J,LI H,MENG C,CHEN D,CHEN Z,WANG Y,et al.Inhibitory effects of omega-3 fatty acids on early brain injury after subarachnoid hemorrhage in rats:possible involvement of G protein-coupled receptor 120/β-arrestin2/TGF-β activated kinase-1 binding protein-1 signaling pathway[J].Int J Biochem Cell Biol,2016,75(5):11-22.
[7] REN Z,CHEN L,WANG Y,WEI X,ZENG S,ZHENG Y,et al.Activation of the omega-3 fatty acid receptor GPR120 protects against focal cerebral ischemic injury by preventing inflammation and apoptosis in mice[J].J Immunol,2019,202(3):747-759.
[8] ZHANG M,QIU S.Activation of GPR120 promotes the metastasis of breast cancer through the PI3K/Akt/NF-κB signaling pathway[J].Anticancer Drugs,2019,30(3):260-270.
[9] 印佳.Omega-3不饱和脂肪酸通过GPR120/β2-arrestin/TAK1/TAB1信号通路对大鼠蛛网膜下腔出血后早期脑损伤的抑制作用及其分子机制的研究[D].苏州:苏州大学,2017.
YIN J.Inhibitory effects of omega-3 fatty acids on early brain injury after subarachnoid hemorrhage in rats:possible involvement of G protein-coupled receptor 120/β-arrestin2/TGF-β activated kinase-1 binding protein-1 signaling pathway[D].Suzhou:Suzhou University,2017.
[10] DTILO M N,SANT’ANA M R,FORMIGARI G P,RODRIGUES P B,DE MOURA L P,DA SILVA A S R,et al.Omega-3 from flaxseed oil protects obese mice against diabetic retinopathy through GPR120 receptor[J].Sci Rep,2018,8(1):14318-14324.
[11] JIANG B,GENG Q,LI T,MOHAMMAD FIRDOUS S,ZHOU X.Morin attenuates STZ-induced diabetic retinopathy in experimental animals[J].Saudi J Biol Sci,2020,27(8):2139-2142.
[12] MADRAKHIMOV S B,YANG J Y,KIM J H,HAN J W,PARK T K.mTOR-dependent dysregulation of autophagy contributes to the retinal ganglion cell loss in streptozotocin-induced diabetic retinopathy[J].Cell Commun Signal,2021,19(1):29-46.
[13] SATAPATI S,QIAN Y,WU M S,PETROV A,DAI G,WANG S P,et al.GPR120 suppresses adipose tissue lipolysis and synergizes with GPR40 in antidiabetic efficacy[J].J Lipid Res,2017,58(8):1561-1578.
[14] PU H,JIANG X,HU X,XIA J,HONG D,ZHANG W,et al.Delayed docosahexaenoic acid treatment combined with dietary supplementation of omega-3 fatty acids promotes long-term neurovascular restoration after ischemic stroke[J].Transl Stroke Res,2016,7(6):521-534.
[15] 王英,吴会平,王冬冬,刘学政.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.
WANG Y,WU H P,WANG D D,LIU X Z.Protective effect of recombinant basic fibroblast growth factor on retinal ganglion cells of diabetic rats through Notch1 Signaling Pathway[J].Rec Adv Ophthalmol,2019,39(10):911-915.
[16] PENG Z,ZHANG C,YAN L,ZHANG Y,YANG Z,WANG J,et al.PA is more effective than DHA to improve depression-like behavior,glia cell dysfunction and hippcampal apoptosis signaling in a chronic stress-induced rat model of depression[J].Int J Mol Sci,2020,21(5):1769-1785.
[17] TUOWIECKA N,KOTLEGA D,PROWANS P,SZCZUKO M.The role of resolvins:EPA and DHA derivatives can be useful in the prevention and treatment of ischemic stroke[J].Int J Mol Sci,2020,21(20):7628-7641.
[18] ZHANG X,MACIELAG M J.GPR120 agonists for the treatment of diabetes:a patent review (2014 present)[J].Expert Opin Ther Pat,2020,30(10):729-742.
[19] FELL G L,CHO B S,DAO D T,ANEZ-BUSTILLOS L,BAKER M A,NANDIVADA P,et al.Fish oil protects the liver from parenteral nutrition-induced injury via GPR120-mediated PPARγ signaling[J].Prostaglandins Leukot Essent Fatty Acids,2019,143(4):8-14.
[20] WELLHAUSER L,BELSHAM D D.Activation of the omega-3 fatty acid receptor GPR120 mediates anti-inflammatory actions in immortalized hypothalamic neurons[J].J Neuroinflammation,2014,11(3):60-65.
[21] OH D Y,WALENTA E,AKIYAMA T E,LAGAKOS W S,LACKEY D,PESSENTHEINER A R,et al.A GPR120-selective agonist improves insulin resistance and chronic inflammation in obese mice[J].Nat Med,2014,20(8):942-947.
[22] CHITRANJALI T,ANOOP CHANDRAN P,MURALEEDHARA KURUP G.Omega-3 fatty acid concentrate from Dunaliella salina possesses anti-inflammatory properties including blockade of NF-κB nuclear translocation[J].Immunopharmacol Immunotoxicol,2015,37(1):81-89.

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备注/Memo

备注/Memo:
国家自然科学基金资助(编号:81571383);辽宁省教育厅课题(编号:L2015324)
更新日期/Last Update: 2021-10-05