[1]於亭,宋继科,魏慧霞,等.电针干预后透镜诱导型近视豚鼠巩膜形态改变及缺氧诱导因子-1α(HIF-1α)和脯氨酰羟化酶2(PHD-2)表达的变化[J].眼科新进展,2021,41(2):125-129.[doi:10.13389/j.cnki.rao.2021.0026]
　YU Ting,SONG Jike,WEI Huixia,et al.Morphological changes of the sclera after electroacupuncture intervention and the expression of hypoxia inducible factor-1α and proline hydroxylase domain-2 in sclera of lens-induced myopic guinea pigs[J].Recent Advances in Ophthalmology,2021,41(2):125-129.[doi:10.13389/j.cnki.rao.2021.0026]
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电针干预后透镜诱导型近视豚鼠巩膜形态改变及缺氧诱导因子-1α(HIF-1α)和脯氨酰羟化酶2(PHD-2)表达的变化/HTML
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《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
41卷
期数:
2021年2期
页码:
125-129
栏目:
实验研究
出版日期:
2021-02-05

文章信息/Info

Title:
Morphological changes of the sclera after electroacupuncture intervention and the expression of hypoxia inducible factor-1α and proline hydroxylase domain-2 in sclera of lens-induced myopic guinea pigs
作者:
於亭; 宋继科; 魏慧霞; 田庆梅; 纪海峰; 毕宏生; 解孝锋
250014　山东省济南市，山东中医药大学（於亭，魏慧霞，纪海峰）； 250002　山东省济南市，山东中医药大学附属眼科医院（宋继科，田庆梅，毕宏生,解孝锋）； 250002　山东省济南市，山东中医药大学眼科研究所；山东省中西医结合眼病防治重点实验室；山东省高校中西医结合眼病防治技术（强化）重点实验室（毕宏生）
Author(s):
YU Ting1; SONG Jike2; WEI Huixia1; TIAN Qingmei2; JI Haifeng1; BI Hongsheng2; 3; XIE Xiaofeng2
1.Shandong University of Traditional Chinese Medicine
2.Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine
3.Eye Institute of Shandong University of Traditional Chinese Medicine； Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases in Universities of Shandong
关键词:
电针; 透镜诱导型近视; 巩膜; 缺氧诱导因子-1α; 脯氨酰羟化酶2
Keywords:
electroacupuncture;  lens-induced myopia;  sclera;  hypoxia induciblefactor-1α;  proline hydroxylase domain-2
分类号:
R778.1
DOI:
10.13389/j.cnki.rao.2021.0026
文献标志码:
A
摘要:
目的　探讨电针干预后透镜诱导型近视(LIM)豚鼠巩膜形态变化及巩膜中缺氧诱导因子-1α（HIF-1α）和脯氨酰羟化酶2(PHD-2)表达变化。方法　将90只2周龄豚鼠随机分为正常对照（NC）组、LIM组和电针+透镜诱导型近视（LIM+EA）组，每组30只。NC组正常饲养，不干预；LIM组和LIM+EA组豚鼠右眼配戴-6.0 D透镜片，建立近视模型；LIM+EA组戴镜同时给予针刺合谷穴和太阳穴30 min。造模后2周和4周测量各组豚鼠的屈光度和眼轴长度，同时通过实时荧光定量PCR（q-PCR）和酶联免疫吸附实验(ELISA)检测各组豚鼠巩膜中HIF-1α和PHD-2的mRNA相对表达及蛋白含量。另外，于造模后4周利用电镜观察各组豚鼠巩膜超微结构变化。结果　造模后2周和4周，与NC组［（2.20±0.48）D、（1.63±0.41）D；（8.22±0.03）mm、（8.40±0.04）mm］相比，LIM组［（-4.23±0.43）D、（-5.88±0.49）D；（8.36±0.05）mm、（8.57±0.06）mm］和LIM+EA组［（-3.63±0.49）D、（-2.55±0.48）D；（8.32±0.03）mm、（8.51±0.03）mm］豚鼠右眼屈光度均增加，眼轴均延长（均为P<0.05）;与LIM组相比，LIM+EA组豚鼠右眼屈光度均减小，眼轴延长均减慢（均为P<0.05）。电镜观察结果显示，与NC组［（82.94±26.03）nm］相比，LIM组［（48.90±23.38）nm］和LIM+EA组［（62.83±21.72）nm］豚鼠巩膜胶原纤维直径变小（均为P<0.05）；与LIM组相比，LIM+EA组巩膜胶原纤维直径变大（P<0.05）。q-PCR及ELISA检测结果表明,造模后2周和4周，与NC组相比，LIM组后极部巩膜HIF-1α mRNA和蛋白表达水平均增加(均为P<0.05),PHD-2 mRNA和蛋白表达水平均下降(均为P<0.05)；与LIM组相比，LIM+EA组巩膜HIF-1α mRNA和蛋白表达水平均显著下降（均为P<0.05），PHD-2 mRNA和蛋白表达水平均上升(均为P<0.05)。结论　电针干预近视豚鼠可影响巩膜胶原纤维直径及HIF-1α和PHD-2的表达水平，进而延缓近视的发展。
Abstract:
Objective　To investigate the morphological changes of the sclera and the expression of scleral hypoxia inducible factor-1α (HIF-1α) and proline hydroxylase domain-2 (PHD-2) in lens-induced myopia (LIM) guinea pigs after electroacupuncture (EA) intervention.Methods　Totally 90 guinea pigs (two-week-old) were randomly divided into normal control (NC) group, LIM group and LIM+EA group, 30 pigs per group. The NC group was fed normally without intervention. The right eye of the LIM and LIM+EA groups were raised with a -6D lens to induce myopia. Meanwhile, the LIM+EA group were treated by EA stimulation at acupoints at Hegu and temples for 30 minutes. After 2 weeks and 4 weeks of the experiment, the refraction and the axial length of guinea pigs from three groups were measured. At the same time, the mRNA and protein expression of HIF-1α and PHD-2 in sclera were detected by real-time fluorescent quantitative PCR (q-PCR) and enzyme-linked immunosorbent assay (ELISA). In addition, the changes of scleral ultrastructure were detected by transmission electron microscopy at 4 weeks.Results　After 2 and 4 weeks, compared with the NC group ［(2.2±0.48) D, (1.63±0.41) D; (8.22±0.03) mm, (8.40±0.04) mm］, the refraction and axial length of the right eye in the LIM group ［(-4.23±0.43) D, (-5.88±0.49) D; (8.36±0.05) mm, (8.57±0.06) mm］ and LIM+EA group ［(-3.63±0.49) D, (-2.55±0.48) D; (8.32±0.03) mm, (8.51±0.03) mm］ were increased (all P<0.05). Compared with the LIM group, the refraction and axial length of the right eye in the LIM+EA group was decreased (all P<0.05). The transmission electron microscopy of sclera results showed that the diameter of scleral collagen fibers in the LIM group ［(48.9±23.38) nm］ and LIM+EA group ［(62.83±21.72) nm］ was smaller than that in NC group ［(82.94±26.03) nm］ (all P<0.05). Compared with the LIM group, the diameter of scleral collagen fibers in the LIM+EA group became larger (P<0.05). The results of q-PCR and ELISA showed that compared with the NC group, the mRNA and protein expression of HIF-1α level in sclera of the LIM group and LIM+EA group were increased (all P<0.05), and the mRNA and protein expression of PHD-2 in sclera of the LIM group and LIM+EA group were decreased (all P<0.05). Compared with the LIM group, the mRNA and protein expression of HIF-1α in sclera in the LIM+EA group were significantly decreased (all P<0.05), and the mRNA and protein expression of PHD-2 were increased (all P<0.05).Conclusion　Electroacupuncture intervention in myopic guinea pigs can affect the diameter of scleral collagen fibers and the expression levels of HIF-1α and PHD-2 and can delay the development of myopia.

参考文献/References:

［1］　HOLDEN B A,FRICKE T R,WILSON D A,JONG M,NAIDOO K S,SANKARIDURG P,et al.Global prevalence of myopia and high myopia and temporal trends from 2000 through 2050［J］.Ophthalmology,2016,123(5):1036-1042.
［2］　MCBRIEN N A,CORNEII L M,GENTLE A.Structural and ultrastructural changes to the sclera in a mammalian model of high myopia［J］.Invest Ophthalmol Vis Sci,2001,42(10):2179-2187.
［3］　WU H,CHEN W,ZHAO F,ZHOU Q Y,REINACH P S,DENG L L,et al.Scleral hypoxia is a target for myopia control［J］.Proc Natl Acad Sci USA,2018,115(30):E7091-E7100.
［4］　訾迎新，邓宇，冀美琦，秦亚丽，金明.形觉剥夺性高度近视豚鼠巩膜形态改变及缺氧诱导因子-1α和氧自由基在高度近视中的作用［J］.眼科新进展,2019,39(8):723-727.
ZI Y X,DENG Y,JI M Q,QIN Y L,JIN M.Changes of scleral morphology in guinea pigs with form deprivation high myopia and effects of hypoxia inducible factor-1α and oxygen free radical in high myopia ［J］.Rec Adv Ophthalmol，2019,39(8):723-727.
［5］　张鸿升，魏卫兵，周宾宾，崔俊武，李振兴，王永清.电针干预脊髓损伤大鼠受损节段缺氧诱导因子1α、血管内皮生长因子的表达［J］.中国组织工程研究,2020,24(11):1701-1707.
ZHANG H S,WEI W B,ZHOU B B,CUI J W,LI Z X,WANG Y Q.Effect of electroacupuncture intervention on expression of hypoxia-inducible factor-1 alpha and vascular endothelial growth factor in injured segments of rats with spinal cord injury ［J］.J Clin Rehabilit Tissue Engin Res,2020,24(11):1701-1707.
［6］　WEI M L，LIU J P，LI N，LIU M.Acupuncture for slowing the progression of myopia in children and adolescents［J］.Cochrane Database Syst Rev,2011,9(9):CD007842.
［7］　YANG X M，XU L Y，ZHONG F，ZHU Y.Data mining-based detection of acupuncture treatment on juvenile myopia［J］.J Tradit Chin Med,2012,32(3):372-376.
［8］　LU F,ZHOU X,JIANG L,FU Y,LAI X,XIE R,et al.Axial myopia induced by hyperopic defocus in guinea pigs:A detailed assessment on susceptibility and recovery［J］.Exp Eye Res,2009,89(1):101-108.
［9］　田庆梅，宋继科，钱继存，李洋，吴姗姗，毕宏生.针刺对实验性近视豚鼠巩膜MMP-2及TIMP-2表达的影响［J］.中华中医药杂志,2019,34(5):2046-2050.
TIAN Q M,SONG J K,QIAN J C,LI Y,WU S S,BI H S.Effects of acupuncture on the expression of MMP-2 and TIMP-2 in experimental myopia guinea pig［J］.China J Tradit Chin Med Pharm,2019,34(5):2046-2050.
［10］　EI-INIMRI N W,YAO M,HUERTA A,HOANG M,WILDSOET C F.Effect of chronic topical latanoprost on the sclera and lamina cribrosa of form-deprived myopic guinea pigs［J］.Exp Eye Res,2019,186:107740.
［11］　GUO Y,XIAO Z,YANG L,GAO Y L,ZHU Q J,HU L J,et al.Hypoxia-inducible factors in hepatocellular carcinoma ［J］.Oncol Rep,2020,43(1):3-15.
［12］　夏冰清，杨帆，张硕，邱雪杉.脯氨酰羟化酶研究进展及其与肿瘤的关系［J］.南通大学学报(医学版),2010,30(2):142-145，147.
XIA B Q,YANG F,ZHANG S,QIU X S.Research progress of prolyl hydroxylase and its relationship with tumors ［J］.J Nantong Univ (Med Sci),2010,30(2):142-145，147.
［13］　张雪，张庆莲.针刺治疗青少年近视52例［J］.长春中医药大学学报,2007,23(1):56.
ZHANG X,ZHANG Q L.Acupuncture for 52 cases of juvenile myopia［J］.J Changchun Univ Chin Med,2007,23(1):56.
［14］　陶晓雁，茹凯，郎松，朱文莲，付娇，陈婧，等.针刺眼周奇穴治疗青少年近视疗效观察［J］.上海针灸杂志,2010,29(10):643-645.
TAO X Y,RU K,LANG S,ZHU W L,FU J,CHEN J,et al.Observations on the efficacy of acupuncture at periocular extraordinary pointsin treating juvenile myopia［J］.Shanghai J Acupunct Moxibust,2010,29(10):643-645.
［15］　吴姗姗，魏慧霞，郭滨，殷学伟，刘德政，郭大东，等.电针对负透镜诱导型近视豚鼠睫状肌中表皮生长因子及其受体表达的作用［J］.眼科新进展,2020,40(4):318-322.
WU S S,WEI H X,GUO B,YIN X W,LIU D Z,GUO D D,et al.Effect of electroacupuncture on expression of epidermal growth factor and its receptor in ciliary muscle of lens-induced myopic guinea pigs［J］.Rec Adv Ophthalmol,2020,40(4):318-322.
［16］　袁野.眼三针配合耳穴治疗青少年近视短期疗效观察［D］.成都：成都中医药大学,2016.
YUAN Y.The short-term clinical efficacy of Jin’s eye three-needle combining with auricular point in treating juvenile myopia［D］.Chengdu：Chengdu University of Traditional Chinese Medicine,2016.
［17］　王晶,尹改珍.头电针加体针治疗青少年脾虚型轻中度近视临床观察［J］.新疆中医药,2017,35(4):45-47.
WANG J,YIN G Z.Clinical observation on scalp electroacupuncture plus body acupuncture for the treatment of mild to moderate myopia with spleen deficiency［J］.Xinjiang Traditi Chin Med,2017,35(4):45-47.

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备注/Memo

备注/Memo:
国家重点研发计划项目（编号：2019YFC1710200、2019YFC1710204）；山东省医药科技发展计划项目（编号：2019WS570）；中国博士后科学基金第67批面上自主项目（编号：2020M672127）
更新日期/Last Update: 2021-02-05