[1]郝一宪,李土玲,魏慧霞,等.电针干预对透镜诱导型近视豚鼠睫状肌中MMP-3、TIMP-3及Col3α1表达的影响[J].眼科新进展,2021,41(8):706-711.[doi:10.13389/j.cnki.rao.2021.0147]
　HAO Yixian,LI Tuling,WEI Huixia,et al.Effects of electroacupuncture on the expression of matrix metalloproteinase-3, tissue inhibitor of metalloproteinase-3 and type III alpha 1 collagen in the ciliary muscle of guinea pigs with lens-induced myopia[J].Recent Advances in Ophthalmology,2021,41(8):706-711.[doi:10.13389/j.cnki.rao.2021.0147]
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电针干预对透镜诱导型近视豚鼠睫状肌中MMP-3、TIMP-3及Col3α1表达的影响/HTML
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《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
41卷
期数:
2021年8期
页码:
706-711
栏目:
实验研究
出版日期:
2021-08-05

文章信息/Info

Title:
Effects of electroacupuncture on the expression of matrix metalloproteinase-3, tissue inhibitor of metalloproteinase-3 and type III alpha 1 collagen in the ciliary muscle of guinea pigs with lens-induced myopia
作者:
郝一宪; 李土玲; 魏慧霞; 刘金鹏; 郭大东; 毕宏生
250355　山东省济南市，山东中医药大学（郝一宪，李土玲，刘金鹏）； 250002　山东省济南市，山东中医药大学附属眼科医院（魏慧霞，毕宏生）； 250002　山东省济南市，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、山东中医药大学眼科研究所（郭大东，毕宏生）
Author(s):
HAO Yixian1;  LI Tuling1;  WEI Huixia2;  LIU Jinpeng1;  GUO Dadong3;  BI Hongsheng2; 3
1.Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
2.Ophthalmic Hospital Affiliated to Shandong University of Traditional Chinese Medicine, Jinan 250002, Shandong Province, China
3.Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Jinan 250002, Shandong Province, China
关键词:
基质金属蛋白酶-3; 金属蛋白酶组织抑制剂-3; III型胶原α1; 电针; 透镜诱导型近视; 睫状肌
Keywords:
matrix metalloproteinase-3;  tissue inhibitor of metalloproteinase-3;  type III alpha 1 collagen;  electroacupuncture;  lens-induced myopia;  ciliary muscle
分类号:
R778.1
DOI:
10.13389/j.cnki.rao.2021.0147
文献标志码:
A
摘要:
目的　探讨电针干预对透镜诱导型近视豚鼠睫状肌中基质金属蛋白酶（MMP）-3、金属蛋白酶组织抑制剂（TIMP）-3和III型胶原α1（Col3α1）表达的影响。方法　2周龄三色豚鼠90只随机分为正常对照（NC）组、透镜诱导型近视（LIM）组以及LIM+电针干预（LIM+EA）组；其中，NC组豚鼠不作任何干预，LIM组和LIM+EA组豚鼠右眼均配戴-6.00 D透镜作为造模眼，左眼不戴镜作为自身对照；LIM+EA组豚鼠右眼戴镜的同时在太阳、合谷穴给予电针刺激。各组豚鼠于造模后1周、2周和4周均进行屈光度和眼轴长度测量，制备病理组织切片观察各组豚鼠睫状肌的形态变化，并应用q-PCR和酶联免疫吸附实验（ELISA）检测各组豚鼠睫状肌中MMP-3、TIMP-3和Col3α1的 mRNA及蛋白表达。结果　造模后1周、2周和4周，与NC组相比，LIM组豚鼠造模眼与自身对照眼近视屈光度和眼轴长度的差值均显著增加（均为P<0.001）；与LIM组相比，LIM+EA组造模眼与自身对照眼近视屈光度和眼轴长度的差值均减小（均为P<0.05）。病理组织切片结果发现，NC组豚鼠睫状肌纤维排列均匀、紧密有序；LIM组豚鼠睫状肌纤维排列松散混乱、有机纤维溶解断裂；LIM+EA组豚鼠睫状肌纤维排列相较于LIM组更为有序，相对完整。q-PCR和ELISA检测结果显示，造模后1周和2周，与NC组相比,LIM组豚鼠造模眼睫状肌中MMP-3、TIMP-3和Col3α1 mRNA及蛋白相对表达水平均明显升高（均为P<0.05）；与LIM组相比，LIM+EA组豚鼠造模眼睫状肌中MMP-3、TIMP-3和Col3α1 mRNA及蛋白相对表达水平均明显下降（均为P<0.05）。造模后4周，与NC组相比,LIM组豚鼠造模眼睫状肌中MMP-3、TIMP-3和Col3α1 mRNA及蛋白相对表达水平均降低（均为P<0.05）；与LIM组相比，LIM+EA组豚鼠造模眼睫状肌中MMP-3、TIMP-3和Col3α1 mRNA及蛋白相对表达水平均升高（均为P<0.05）。结论　近视发展初期，电针干预可显著下调透镜诱导型近视豚鼠睫状肌中MMP-3、TIMP-3和Col3α1的表达，明显延缓近视的发生发展。
Abstract:
Objective　To investigate the effect of electroacupuncture on the expression of matrix metalloproteinase-3 (MMP-3), tissue inhibitor of metalloproteinase-3 (TIMP-3) and type III alpha (1) collagen (Col3α1) in the ciliary muscle of guinea pigs with lens-induced myopia.Methods　Ninety 2-week-old tricolor guinea pigs were randomly divided into the normal control (NC) group, lens-induced myopia (LIM) group and lens-induced myopia+electroacupuncture (LIM+EA) group. Guinea pigs in the NC group did not receive any intervention, while the right eyes of guinea pigs in the LIM and LIM+EA groups wore -6.00 D lens as model eyes, and the left eyes did not wear any lens as self-control eyes. Besides, guinea pigs in the LIM + EA group received electroacupuncture at Taiyang and Hegu acupoints. The diopter and axial length of guinea pigs in each group were measured at week 1, 2 and 4 after modeling. Pathological tissue sections were prepared to observe the morphological changes of the ciliary muscle, and the mRNA and protein expression of MMP-3, TIMP-3 and Col3α1 in the ciliary muscle were detected by quantitative polymerase chain reaction (q-PCR) and enzyme linked immunosorbent assay (ELISA), respectively.Results　At week 1, 2 and 4 after modeling, the difference of diopter and axial length between the model eyes (right eyes) and the self-control eyes (left eyes) in the LIM group was significantly higher than that in the NC group (all P<0.001), while the difference of diopter and axial length between the model eyes and the self-control eyes in the LIM+EA group was lower than that in the LIM group (all P<0.05). Pathological tissue sections showed that the ciliary muscle fibers of guinea pigs in the NC group were arranged uniformly and tightly, while the arrangement in the LIM group was loose and chaotic, and the organic fibers were dissolved and broken. Compared with the LIM group, ciliary muscle fibers in the LIM+EA group were arranged more orderly and completely. The q-PCR and ELISA results showed that, at week 1 and 2 after modeling, the mRNA and protein expression levels of MMP-3, TIMP-3 and Col3α1 in the ciliary muscle of guinea pigs in the LIM group were significantly higher than those in the NC group (all P<0.05), and the mRNA and protein expression levels of MMP-3, TIMP-3 and Col3α1 in the LIM+EA group were significantly lower than those in the LIM group (all P<0.05). At week 4 after modeling, the mRNA and protein relative expression levels of MMP-3, TIMP-3 and Col3α1 in the ciliary muscle of guinea pigs in the LIM group were lower than those in the NC group (all P<0.05), and the mRNA and protein expression levels of MMP-3, TIMP-3 and Col3α1 in the LIM+EA group were higher than those in the LIM group (all P<0.05).Conclusion　In the early stage of myopia, electroacupuncture can significantly reduce the expression levels of MMP-3, TIMP-3 and Col3α1 in the ciliary muscle of guinea pigs with lens-induced myopia, delaying the development of myopia.

参考文献/References:

［1］　MORGAN I G,FRENCH A N,ASHBY R S,GUO X,DING X,HE M,et al.The epidemics of myopia:aetiology and prevention［J］.Prog Retin Eye Res，2018，62:134-149.
［2］　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.
［3］　AGGARWALA K R G.Ocular accommodation,intraocular pressure,development of myopia and glaucoma:role of ciliary muscle,choroid and metabolism［J］.Med Hypothesis Discov Innov Ophthalmol，2020，9(1):66-70.
［4］　CHEN J C,SCHMID K L,BROWN B.The autonomic control of accommodation and implications for human myopia development:a review［J］.Ophthalmic Physiol Opt，2003，23(5):401-422.
［5］　WEINREB R N,LINDSEY J D,LUO X X,WANG T H.Extracellular matrix of the human ciliary muscle［J］.J Glaucoma，1994，3(1):70-78.
［6］　ZHOU X,QU J,XIE R,WANG R,JIANG L,ZHAO H,et al.Normal development of refractive state and ocular dimensions in guinea pigs［J］.Vision Res，2006，46(18):2815-2823.
［7］　MORGAN I,ROSE K.How genetic is school myopia? ［J］.Prog Retin Eye Res， 2005，24(1):1-38.
［8］　VASUDEVAN B,CIUFFREDA K J.Additivity of near work-induced transient myopia and its decay characteristics in different refractive groups［J］.Invest Ophthalmol Vis Sci，2008，49(2):836-841.
［9］　欧丽蓉,保金华,汪育文,吕帆.近视儿童阅读行为及其相关因素的研究［J］.中华眼视光学与视觉科学杂志，2008，10(2):84-88.
OU L R,BAO J H,WANG Y W,L F.Research on reading behavior and related factors of myopic children［J］.Chin J Optom Ophthalmol Vis Sci，2008，10(2):84-88.
［10］　PUCKER A D,JACKSON A R,MCHUGH K M,MUTTI D O.Morphological ciliary muscle changes associated with form deprivation-induced myopia［J］.Exp Eye Res，2020，193:107963.
［11］　OH D J,MARTIN J L,WILLIAMS A J,PECK R E,POKORNY C,RUSSELL P,et al.Analysis of expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human ciliary body after latanoprost［J］.Invest Ophthalmol Vis Sci，2006，47(3):953-963.
［12］　WANG J C.Importance of plasma matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinase (TIMP) in development of fibrosis in agnogenic myeloid metaplasia［J］.Leuk Lymphoma，2005，46(9):1261-1268.
［13］　SIEGWART J T Jr,NORTON T T.Selective regulation of MMP and TIMP mRNA levels in tree shrew sclera during minus lens compensation and recovery［J］.Invest Ophthalmol Vis Sci，2005，46(10):3484-3492.
［14］　VALIMAKI J,UUSITALO H.Matrix metalloproteinases (MMP-1,MMP-2,MMP-3 and MMP-9,and TIMP-1,TIMP-2 and TIMP-3) and markers for vascularization in functioning and non-functioning bleb capsules of glaucoma drainage implants［J］.Acta Ophthalmol，2015，93(5):450-456.
［15］　KUIVANIEMI H,TROMP G.Type III collagen (COL3A1):gene and protein structure,tissue distribution,and associated diseases［J］.Gene，2019，707:151-171.
［16］　JIA Y,HU D N,ZHU D,ZHANG L,GU P,FAN X,et al.MMP-2,MMP-3,TIMP-1,TIMP-2,and TIMP-3 protein levels in human aqueous humor:relationship with axial length［J］.Invest Ophthalmol Vis Sci，2014，55(6):3922-3928.
［17］　JIA Y,YUE Y,HU D N,CHEN J L,ZHOU J B.Human aqueous humor levels of transforming growth factor-beta2:association with matrix metalloproteinases/tissue inhibitors of matrix metalloproteinases［J］.Biomed Rep，2017，7(6):573-578.
［18］　张煜,魏然,黄萍,贾茜雅,熊丽霞.Cdc42作为功能性因子调控纤维化［J］.中国细胞生物学学报，2017，39(3):348-355.
ZHANG Y,WEI R,HUANG P,JIA Q Y,XIONG L X.Cdc42 as a functional meditation factor in fibrosis［J］.Chin J Cell Biol，2017，39(3):348-355.
［19］　MARIA A T J,BOURGIER C,MARTINAUD C,BORIE R,ROZIER P,RIVIRE S,et al.From fibrogenesis towards fibrosis:pathophysiological mechanisms and clinical presentations ［J］.Rev Med Interne，2020，41(5):325-329.
［20］　YAMANAKA O,LIU C Y,KAO W W.Fibrosis in the anterior segments of the eye［J］.Endocr Metab Immune Disord Drug Targets，2010，10(4):331-335.
［21］　GREENE W,BURKE T,BRAMBLETT G,WANG H C.Detection of retinal fibrosis in a rabbit model of penetrating eye injury［J］.Mil Med，2020，185(Suppl 1):443-447.
［22］　MILIVOJEVIC M,VUKOSAVLJEVIC M,ALEKSIC P,STOJKOVIC R,DIMITRIJEVIC J,LATKOVIC Z,et al.Comparison of the suppressing capecitabine and 5-fluorouracil effects on the pronounce of inflammatory cells score in the induction of episcleral fibrosis after trabeculectomy ［J］.Vojnosanit Pregl，2007，64(7):449-452.
［23］　ZEISBERG M,KALLURI R.Cellular mechanisms of tissue fibrosis.1.Common and organ-specific mechanisms associated with tissue fibrosis［J］.Am J Physiol Cell Physiol，2013，304(3):C216-225.
［24］　CRAIG V J,ZHANG L,HAGOOD J S,OWEN C A.Matrix metalloproteinases as therapeutic targets for idiopathic pulmonary fibrosis［J］.Am J Respir Cell Mol Biol，2015，53(5):585-600.
［25］　SELMAN M,RUIZ V,CABRERA S,SEGURA L,RAMIREZ R,BARRIOS R,et al.TIMP-1,-2,-3,and -4 in idiopathic pulmonary fibrosis.A prevailing nondegradative lung microenvironment? ［J］.Am J Physiol Lung Cell Mol Physiol，2000，279(3):L562-574.
［26］　CHEN X,LI X F,CHEN Y,ZHU S,LI H D,CHEN S Y,et al.Hesperetin derivative attenuates CCl4-induced hepatic fibrosis and inflammation by Gli-1-dependent mechanisms［J］.Int Immunopharmacol，2019，76:105838.
［27］　CHEN B Y,WANG C Y,CHEN W Y,MA J X.Altered TGF-β2 and bFGF expression in scleral desmocytes from an experimentally-induced myopia guinea pig model［J］.Graefes Arch Clin Exp Ophthalmol，2013，251(4):1133-1144.

备注/Memo

备注/Memo:
国家重点研发计划项目（编号：2019YFC1710200）；山东省重点研发计划项目（编号： 2019GSF108252,2017CXGC1211）
更新日期/Last Update: 2021-08-05