【《耳蜗的结构与功能研究文献综述》7200字】

耳蜗的结构与功能研究文献综述1耳的结构人耳能够分辨不同强度、不同频率的声音信号。从耳边的轻声细语到汽车鸣笛的声音，均能够被人耳捕捉、分析并将其传递到大脑产生听觉；另一方面，人耳能够分辨不同频率（从20Hz到20kHz）的声音信号，从而能欣赏美妙的音乐旋律。人耳能够实现对于不同外界声音刺激的精确感知和解析，这与其自身复杂而精巧的结构密不可分。ADDINEN.CITEADDINEN.CITE.DATA(\o"Frolenkov,2004#1286"Frolenkovetal.,2004;\o"Hudspeth,1997#1905"Hudspeth,1997a)耳是哺乳动物感受听觉和保持平衡的器官。耳分为外耳（externalear）、中耳（middleear）和内耳（innerear）三部分（REF_Ref65934775\h图1.1a），外耳由耳廓（auricle）和外耳道（earcanal）组成，后者经鼓膜（tympanicmembrane）与中耳分隔开，中耳包括鼓室（tympaniccavity）和鼓膜，位于鼓室内的锤骨（malleus）、砧骨（incus）和镫骨（stapes）三个听小骨（ossicles）形成听骨链，将鼓膜的振动传导至内耳。内耳和中耳通过圆窗和卵圆窗相连，两者均覆盖透明且富有弹性的膜状结构。其中卵圆窗膜与组成听骨链的镫骨足板相连，能够感受来自镫骨的振动压力。内耳（innerear）是人耳结构最复杂精妙功能最强大的部分，包含耳蜗（cochlea）和前庭（vestibule）两部分。其中耳蜗是人体的声音感受器，负责感知外界声音刺激。耳廓能够收集来自环境的声音刺激，外耳道将其传递到鼓膜，引起鼓膜振动，随后三个听小骨将鼓膜的振动依次传导至耳蜗，通过毛细胞将振动产生的机械信号转换为神经元能够识别的电信号，最终到达大脑皮层产生听觉。前庭为人体的平衡感受器，能够帮助人体感知头部相对的空间位置和身体应对不同需求的运动状态ADDINEN.CITEADDINEN.CITE.DATA(\o"Frolenkov,2004#1286"Frolenkovetal.,2004)。耳蜗在听觉发生的过程中发挥重要作用，人耳对于声音信号的强度和频率的解析主要依赖耳蜗精巧的生物学结构和作用机制。耳蜗是由三个管状腔系围绕蜗轴螺旋缠绕形成的类似蜗牛壳形状的结构，自上而下分别为前庭阶（scalavestibuli）、中阶（scalamedia）和鼓阶（scalatympani）。组成耳蜗的三个腔系均充满液体，中阶包含的是内淋巴液（endolymph），而前庭阶和鼓阶则充满了外淋巴液（perilymph）。内淋巴液的组成成分与细胞内液类似，其中含有高钾离子、低钠离子浓度的溶液，而外淋巴液的组成成分则与细胞外液相似，其中含有高钠离子、低钾离子浓度的溶液（REF_Ref65934775\h图1.1b）ADDINEN.CITEADDINEN.CITE.DATA(\o"Frolenkov,2004#1286"Frolenkovetal.,2004)。图1.SEQ图1.\*ARABIC1人耳的结构（a）人耳分为外耳（Externalear）、中耳（Middleear）和内耳（Innerear）三部分。其中外耳包括耳廓（Auricle）和外耳道（Earcanal）两部分；中耳包括鼓膜（Tympanicmembrane）和听小骨（Ossicles）；内耳分为前庭（Vestibule）和耳蜗（Cochlea）两部分。（b）耳蜗垂直其延伸方向的横切面示意图。前庭阶：Scalavestibuli；中阶：Scalamedia；鼓阶：Scalatympani。将声音信号转化为电信号的的柯蒂氏器（OrganofCorti）位于中阶内。ADDINEN.CITE<EndNote><Cite><Author>Dror</Author><Year>2009</Year><RecNum>2116</RecNum><DisplayText>(DrorandAvraham,2009)</DisplayText><record><rec-number>2116</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1616121997">2116</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Dror,AmielA.</author><author>Avraham,KarenB.</author></authors></contributors><auth-address>DepartmentofHumanMolecularGeneticsandBiochemistry,SacklerSchoolofMedicine,TelAvivUniversity,TelAviv69978,Israel.amieldro@post.tau.ac.il</auth-address><titles><title>Hearingloss:mechanismsrevealedbygeneticsandcellbiology</title><secondary-title>Annualreviewofgenetics</secondary-title><alt-title>AnnuRevGenet</alt-title></titles><alt-periodical><full-title>AnnuRevGenet</full-title></alt-periodical><pages>411-437</pages><volume>43</volume><dates><year>2009</year></dates><isbn>1545-2948</isbn><accession-num>19694516</accession-num><urls><related-urls><url>/19694516</url><url>/doi/pdf/10.1146/annurev-genet-102108-134135</url></related-urls></urls><electronic-resource-num>10.1146/annurev-genet-102108-134135</electronic-resource-num><remote-database-name>PubMed</remote-database-name><language>eng</language></record></Cite></EndNote>(\o"Dror,2009#2116"DrorandAvraham,2009)2耳蜗的结构与功能通过漫长的进化过程，在哺乳动物的耳蜗中，对于听觉信号的处理和传导形成了一套结构复杂且精密的调控系统ADDINEN.CITE<EndNote><Cite><Author>Hudspeth</Author><Year>1997</Year><RecNum>2114</RecNum><DisplayText>(Hudspeth,1997b)</DisplayText><record><rec-number>2114</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1616121550">2114</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Hudspeth,A.J.</author></authors></contributors><auth-address>HowardHughesMedicalInstitute,TheRockefellerUniversity,NewYork,NewYork10021,USA.</auth-address><titles><title>Howhearinghappens</title><secondary-title>Neuron</secondary-title><alt-title>Neuron</alt-title></titles><periodical><full-title>Neuron</full-title></periodical><alt-periodical><full-title>Neuron</full-title></alt-periodical><pages>947-950</pages><volume>19</volume><number>5</number><dates><year>1997</year></dates><isbn>0896-6273</isbn><accession-num>9390507</accession-num><urls><related-urls><url>/9390507</url></related-urls></urls><remote-database-name>PubMed</remote-database-name><language>eng</language></record></Cite></EndNote>(\o"Hudspeth,1997#2114"Hudspeth,1997b)。哺乳动物与非哺乳类动物相比，虽然参与听觉器官和细胞类型具有较高保守性，却具有更加灵敏的听觉感知能力和频率选择性，这主要依赖哺乳动物耳蜗复杂结构及精密的作用机制ADDINEN.CITEADDINEN.CITE.DATA(\o"Frolenkov,2004#1286"Frolenkovetal.,2004)。因此，接下来将对耳蜗的结构和功能进行了详细的描述。2.1耳蜗的结构与功能耳蜗中阶内的柯蒂氏器（OrganofCorti）能够感受来自外界声音的机械刺激并将其转化为电信号。基底膜（basilarmembrane，BM）和依附其结构行使功能的听觉毛细胞与支持细胞，以及覆盖于毛细胞上方的盖膜共同组成柯蒂氏器。内外毛细胞顶部均有静纤毛，通常整齐排列成三排（REF_Ref67062435\h图1.2）。不同于支持细胞，毛细胞能够将机械刺激转化为神经电信号，这些电信号经螺旋神经节和听神经传递，最终到达大脑ADDINEN.CITEADDINEN.CITE.DATA(\o"Frolenkov,2004#1286"Frolenkovetal.,2004)。图1.SEQ图1.\*ARABIC2耳蜗柯蒂氏器的结构示意图耳蜗中阶柯蒂氏器由盖膜（Tectorialmembrane）和基底膜（Basilarmembrane）组成，基底膜上有规则排布的外毛细胞（Outerhaircells）和内毛细胞（Innerhaircells）。内外毛细胞的顶端有静纤毛（Stereocilia）。ADDINEN.CITEADDINEN.CITE.DATA(\o"Frolenkov,2004#1286"Frolenkovetal.,2004)耳蜗的功能与高度特化的结构密切相关，其对于声音的传导和频率的解析起始于卵圆窗膜感受来自镫骨的压力，这种压力会引起基底膜产生上下振动，并通过柯蒂氏器其他结构的传导和解析最终产生电信号。柯蒂氏器解析声音的过程依赖其特异性的结构，下文借助听觉发生的过程介绍柯蒂氏器的结构与功能特性。耳蜗毛细胞位于基底膜上，基底膜有特殊的结构和机械特性，哺乳动物基底膜沿耳蜗长度连续变化，靠近中耳的底部更窄更薄，但相对更紧实，而靠近蜗孔的顶部更宽更厚，也更松弛。基底膜能够感受来自前庭阶和鼓阶的压力变化并随之上下振动，沿其长度每一个位置都有其对应的特征频率，当该频率振动的波传导接近该位置时，其振幅缓慢增大，并在该位置引起基底膜最大振幅的振动，随后振幅迅速降低，基底膜的这种特性对于声音频率的解析十分重要，即基底膜上特定位置的毛细胞在其对应频率刺激下产生最大振幅（REF_Ref65935193\h图1.3）ADDINEN.CITE<EndNote><Cite><Author>BecharaKachar</Author><Year>2013</Year><RecNum>1941</RecNum><DisplayText>(BecharaKachar,2013)</DisplayText><record><rec-number>1941</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1612860101">1941</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>BecharaKachar,MarianneParakkal,MauricioKurc,Yi-dongZhao,andPeterG.Gillespie</author></authors></contributors><titles><title>High-resolutionstructureofhair-celltiplinks</title><secondary-title>PNAS</secondary-title></titles><periodical><full-title>PNAS</full-title></periodical><pages>12155-12155</pages><volume>110</volume><number>29</number><section>12155</section><dates><year>2013</year></dates><isbn>0027-8424 1091-6490</isbn><urls></urls><electronic-resource-num>10.1073/pnas.1311228110</electronic-resource-num></record></Cite></EndNote>(\o"BecharaKachar,2013#1941"BecharaKachar,2013)。图1.SEQ图1.\*ARABIC3耳蜗基底膜不同位置与频率的对应关系耳蜗基底膜上不同位置的毛细胞对于声音刺激具有频率选择性，其中底部（Base）的毛细胞对高频声音信号特异性响应，而顶部（Apex）的毛细胞对低频声音信号特异性响应。图片引自http://www.cochlea.eu。听觉毛细胞是高度特化的一种感觉细胞，顶部有30～60根毛发状的结构，因此研究人员称之为毛细胞。毛细胞分为内毛细胞（innerhaircell）和外毛细胞（outerhaircell）两种，它们在基底膜上的分布位置不同，内毛细胞仅有一排，距离蜗轴较近；而外毛细胞通常有3~4排，分布在内毛细胞外侧。内外毛细胞顶端的毛发状结构被称为静纤毛（stereocilia），在毛细胞成熟过程中，静纤毛从胞体顶端长出，并逐渐形成特定的排列方式（REF_Ref65935940\h图1.4）ADDINEN.CITE<EndNote><Cite><Author>Schwander</Author><Year>2010</Year><RecNum>1381</RecNum><DisplayText>(Schwanderetal.,2010)</DisplayText><record><rec-number>1381</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1587285426">1381</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Schwander,M.</author><author>Kachar,B.</author><author>Muller,U.</author></authors></contributors><auth-address>DepartmentofCellBiology,DorrisNeuroscienceCenter,TheScrippsResearchInstitute,LaJolla,CA92037,USA.</auth-address><titles><title>Thecellbiologyofhearing</title><secondary-title>JCellBiol</secondary-title></titles><periodical><full-title>JCellBiol</full-title></periodical><pages>9-20</pages><volume>190</volume><number>1</number><edition>2010/07/14</edition><keywords><keyword>Animals</keyword><keyword>Deafness/*genetics/*metabolism</keyword><keyword>HairCells,Auditory,Inner/*metabolism</keyword><keyword>Hearing/*genetics</keyword><keyword>Humans</keyword><keyword>Mechanotransduction,Cellular/*genetics</keyword></keywords><dates><year>2010</year><pub-dates><date>Jul12</date></pub-dates></dates><isbn>1540-8140(Electronic) 0021-9525(Linking)</isbn><accession-num>20624897</accession-num><urls><related-urls><url>/pubmed/20624897</url></related-urls></urls><custom2>PMC2911669</custom2><electronic-resource-num>10.1083/jcb.201001138</electronic-resource-num></record></Cite></EndNote>(\o"Schwander,2010#1381"Schwanderetal.,2010)。图1.SEQ图1.\*ARABIC4耳蜗毛细胞扫描电镜图基底膜上规则排列着三排外毛细胞（OHC）和一排内毛细胞（IHC），毛细胞的顶部有高低依次分布的静纤毛。ADDINEN.CITE<EndNote><Cite><Author>Schwander</Author><Year>2010</Year><RecNum>1381</RecNum><DisplayText>(Schwanderetal.,2010)</DisplayText><record><rec-number>1381</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1587285426">1381</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Schwander,M.</author><author>Kachar,B.</author><author>Muller,U.</author></authors></contributors><auth-address>DepartmentofCellBiology,DorrisNeuroscienceCenter,TheScrippsResearchInstitute,LaJolla,CA92037,USA.</auth-address><titles><title>Thecellbiologyofhearing</title><secondary-title>JCellBiol</secondary-title></titles><periodical><full-title>JCellBiol</full-title></periodical><pages>9-20</pages><volume>190</volume><number>1</number><edition>2010/07/14</edition><keywords><keyword>Animals</keyword><keyword>Deafness/*genetics/*metabolism</keyword><keyword>HairCells,Auditory,Inner/*metabolism</keyword><keyword>Hearing/*genetics</keyword><keyword>Humans</keyword><keyword>Mechanotransduction,Cellular/*genetics</keyword></keywords><dates><year>2010</year><pub-dates><date>Jul12</date></pub-dates></dates><isbn>1540-8140(Electronic) 0021-9525(Linking)</isbn><accession-num>20624897</accession-num><urls><related-urls><url>/pubmed/20624897</url></related-urls></urls><custom2>PMC2911669</custom2><electronic-resource-num>10.1083/jcb.201001138</electronic-resource-num></record></Cite></EndNote>(\o"Schwander,2010#1381"Schwanderetal.,2010)每个毛细胞顶部的静纤毛呈阶梯式规律排布，分为低中高三排，同一高度的一排的静纤毛之间还有许多侧连接，相邻两个高度两排的静纤毛之间由顶连接（tip-link）相连，顶连接与较低一排的静纤毛连接处有机械敏感通道，这样的精妙结构可以使得所有静纤毛的产生方向相同的运动（REF_Ref65936125\h图1.5）ADDINEN.CITEADDINEN.CITE.DATA(\o"Frolenkov,2004#1286"Frolenkovetal.,2004)。图1.SEQ图1.\*ARABIC5外毛细胞顶端静纤毛的微观结构（a）外毛细胞顶端静纤毛扫描电镜图。（b）相邻两排静纤毛之间的顶连接（图中白色箭头所示）扫描电镜图。ADDINEN.CITEADDINEN.CITE.DATA(\o"Frolenkov,2004#1286"Frolenkovetal.,2004)2.2耳蜗毛细胞的机械电转导通道的分子组成与功能耳蜗毛细胞利用位于静纤毛顶端的机械门控离子通道，将声波诱发的基底膜的振动转化成毛细胞膜电位，并进一步通过听神经纤维将电信号传递到大脑听皮层ADDINEN.CITE<EndNote><Cite><Author>Hudspeth</Author><Year>1997</Year><RecNum>2114</RecNum><DisplayText>(Hudspeth,1997b)</DisplayText><record><rec-number>2114</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1616121550">2114</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Hudspeth,A.J.</author></authors></contributors><auth-address>HowardHughesMedicalInstitute,TheRockefellerUniversity,NewYork,NewYork10021,USA.</auth-address><titles><title>Howhearinghappens</title><secondary-title>Neuron</secondary-title><alt-title>Neuron</alt-title></titles><periodical><full-title>Neuron</full-title></periodical><alt-periodical><full-title>Neuron</full-title></alt-periodical><pages>947-950</pages><volume>19</volume><number>5</number><dates><year>1997</year></dates><isbn>0896-6273</isbn><accession-num>9390507</accession-num><urls><related-urls><url>/9390507</url></related-urls></urls><remote-database-name>PubMed</remote-database-name><language>eng</language></record></Cite></EndNote>(\o"Hudspeth,1997#2114"Hudspeth,1997b)，在这个过程，发挥重要功能的是相邻高度的两排静纤毛顶端之间相连接的顶连接（REF_Ref65955155\h图1.6）ADDINEN.CITEADDINEN.CITE.DATA(\o"Basu,2016#1943"Basuetal.,2016;\o"Pickles,1984#2118"Picklesetal.,1984)。研究人员发现，在毛细胞顶连接与静纤毛相连的端点附近，有大量参与毛细胞MET功能的分子（REF_Ref65955155\h图1.6）。其中位于顶连接底端的MET通道附近的TMC1/2对于毛细胞MET功能十分重要，敲除TMC1/2后小鼠耳聋并伴随转圈的表型ADDINEN.CITEADDINEN.CITE.DATA(\o"Kawashima,2011#109"Kawashimaetal.,2011)。此外，Harmonin，SANS和MYOVIIA位于顶连接的上端，与CDH23形成蛋白复合体，调控顶连接的张力及MET通道的开放。LHFPL5，TMIE以及TMC1/2位于静纤毛的顶端，与PCDH15形成蛋白复合体，对于MET通道的功能必不可少。PIP2和CIB2定位于顶连接底端，直接参与静纤毛顶端MET通道的功能。此外，位于胞内的TOMT蛋白通过调控TMC1/2在毛细胞静纤毛顶端的定位也参与到机械电转的过程ADDINEN.CITE<EndNote><Cite><Author>Cunningham</Author><Year>2019</Year><RecNum>1464</RecNum><DisplayText>(CunninghamandMuller,2019)</DisplayText><record><rec-number>1464</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1587816469">1464</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Cunningham,C.L.</author><author>Muller,U.</author></authors></contributors><auth-address>TheSolomonSnyderDepartmentofNeuroscience,JohnsHopkinsUniversity,Baltimore,Maryland21205.</auth-address><titles><title>MolecularStructureoftheHairCellMechanoelectricalTransductionComplex</title><secondary-title>ColdSpringHarbPerspectMed</secondary-title></titles><periodical><full-title>ColdSpringHarbPerspectMed</full-title></periodical><volume>9</volume><number>5</number><edition>2018/08/08</edition><dates><year>2019</year><pub-dates><date>May1</date></pub-dates></dates><isbn>2157-1422(Electronic) 2157-1422(Linking)</isbn><accession-num>30082452</accession-num><urls><related-urls><url>/pubmed/30082452</url></related-urls></urls><electronic-resource-num>10.1101/cshperspect.a033167</electronic-resource-num></record></Cite></EndNote>(\o"Cunningham,2019#1464"CunninghamandMuller,2019)。毛细胞完成的MET功能的分子机制一直是研究人员关注的重点，研究表明毛细胞MET通道是由一系列蛋白组装而成的，但是目前，并没有发现单独能够实现MET通道功能的蛋白，因此对于毛细胞MET通道关键蛋白的鉴定和研究依旧是理解毛细胞该功能的重要前提ADDINEN.CITE<EndNote><Cite><Author>Cunningham</Author><Year>2019</Year><RecNum>1464</RecNum><DisplayText>(CunninghamandMuller,2019)</DisplayText><record><rec-number>1464</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1587816469">1464</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Cunningham,C.L.</author><author>Muller,U.</author></authors></contributors><auth-address>TheSolomonSnyderDepartmentofNeuroscience,JohnsHopkinsUniversity,Baltimore,Maryland21205.</auth-address><titles><title>MolecularStructureoftheHairCellMechanoelectricalTransductionComplex</title><secondary-title>ColdSpringHarbPerspectMed</secondary-title></titles><periodical><full-title>ColdSpringHarbPerspectMed</full-title></periodical><volume>9</volume><number>5</number><edition>2018/08/08</edition><dates><year>2019</year><pub-dates><date>May1</date></pub-dates></dates><isbn>2157-1422(Electronic) 2157-1422(Linking)</isbn><accession-num>30082452</accession-num><urls><related-urls><url>/pubmed/30082452</url></related-urls></urls><electronic-resource-num>10.1101/cshperspect.a033167</electronic-resource-num></record></Cite></EndNote>(\o"Cunningham,2019#1464"CunninghamandMuller,2019)。图1.SEQ图1.\*ARABIC6顶连接的结构示意图顶连接是由两个钙黏蛋白以二聚体的方式相连形成的刚性连接，与较低一排静纤毛顶端MET通道相连的是由两个PCDH15蛋白形成的二聚体，顶连接的另一端由两个CDH23单体形成二聚体与较高一排的静纤毛侧壁连接。ADDINEN.CITE<EndNote><Cite><Author>Cunningham</Author><Year>2019</Year><RecNum>1464</RecNum><DisplayText>(CunninghamandMuller,2019)</DisplayText><record><rec-number>1464</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1587816469">1464</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Cunningham,C.L.</author><author>Muller,U.</author></authors></contributors><auth-address>TheSolomonSnyderDepartmentofNeuroscience,JohnsHopkinsUniversity,Baltimore,Maryland21205.</auth-address><titles><title>MolecularStructureoftheHairCellMechanoelectricalTransductionComplex</title><secondary-title>ColdSpringHarbPerspectMed</secondary-title></titles><periodical><full-title>ColdSpringHarbPerspectMed</full-title></periodical><volume>9</volume><number>5</number><edition>2018/08/08</edition><dates><year>2019</year><pub-dates><date>May1</date></pub-dates></dates><isbn>2157-1422(Electronic) 2157-1422(Linking)</isbn><accession-num>30082452</accession-num><urls><related-urls><url>/pubmed/30082452</url></related-urls></urls><electronic-resource-num>10.1101/cshperspect.a033167</electronic-resource-num></record></Cite></EndNote>(\o"Cunningham,2019#1464"CunninghamandMuller,2019)2.3耳蜗血管纹的结构与功能柯蒂氏器在将声音信号转化为电信号传到大脑听皮层的过程中，不仅需要其自身精巧的结构，还依赖于中阶内环境的稳态。前文提到耳蜗中阶充满高钾低钠的内淋巴液，这与中阶外侧壁（lateralwall，LW）血管纹的结构与功能密切相关ADDINEN.CITE<EndNote><Cite><Author>Zdebik</Author><Year>2009</Year><RecNum>1285</RecNum><DisplayText>(Zdebiketal.,2009)</DisplayText><record><rec-number>1285</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1585990953">1285</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Zdebik,AnselmA.</author><author>Wangemann,Philine</author><author>Jentsch,ThomasJ.</author></authors></contributors><titles><title>PotassiumIonMovementintheInnerEar:InsightsfromGeneticDiseaseandMouseModels</title><secondary-title>Physiology</secondary-title></titles><periodical><full-title>Physiology</full-title></periodical><pages>307-316</pages><volume>24</volume><number>5</number><section>307</section><dates><year>2009</year></dates><isbn>1548-9213 1548-9221</isbn><urls></urls><electronic-resource-num>10.1152/physiol.00018.2009</electronic-resource-num></record></Cite></EndNote>(\o"Zdebik,2009#1285"Zdebiketal.,2009)。血管纹由三层上皮细胞组成，分别发育来自不同的胚胎部位。其中与内淋巴液接触的边缘细胞（marginalcell，MC）来源于耳上皮细胞，中间细胞（intermediatecells，IC）是由神经嵴迁移发育而来的一类特化的黑色素细胞，而位于最外侧的基底细胞（basalcell，BC）则来源于胚胎发育早期围绕在耳囊外侧的间充质干细胞ADDINEN.CITEADDINEN.CITE.DATA(\o"Hilding,1977#1967"HildingandGinzberg,1977;\o"Lang,2007#1911"Langetal.,2007)。血管纹与耳蜗中阶的边界是边缘细胞，与螺旋韧带（spiralligament，SP）相接的是基底细胞。边缘细胞和基底细胞彼此之间都是通过紧密连接形成片层状致密组织，在这两层细胞之间是纹内间隙，内有呈网纹状分布的丰富的毛细血管，以及散布其中的一层不连续的中间细胞。基底细胞和中间细胞以及紧邻的螺旋韧带中的纤维细胞通过间隙连接相连（REF_Ref65955893\h图1.7）ADDINEN.CITE<EndNote><Cite><Author>Zdebik</Author><Year>2009</Year><RecNum>1285</RecNum><DisplayText>(Zdebiketal.,2009)</DisplayText><record><rec-number>1285</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1585990953">1285</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Zdebik,AnselmA.</author><author>Wangemann,Philine</author><author>Jentsch,ThomasJ.</author></authors></contributors><titles><title>PotassiumIonMovementintheInnerEar:InsightsfromGeneticDiseaseandMouseModels</title><secondary-title>Physiology</secondary-title></titles><periodical><full-title>Physiology</full-title></periodical><pages>307-316</pages><volume>24</volume><number>5</number><section>307</section><dates><year>2009</year></dates><isbn>1548-9213 1548-9221</isbn><urls></urls><electronic-resource-num>10.1152/physiol.00018.2009</electronic-resource-num></record></Cite></EndNote>(\o"Zdebik,2009#1285"Zdebiketal.,2009)。图1.SEQ图1.\*ARABIC7耳蜗中阶及血管纹示意图耳蜗中阶由基底膜（basilarmembrane）、血管纹（striavascularis）和前庭膜（Reissner’smembrane）围绕而成的封闭区域，血管纹和基底膜之间向中介突出结构为螺旋突（Sprialprominence）。ADDINEN.CITE<EndNote><Cite><Author>Zdebik</Author><Year>2009</Year><RecNum>1285</RecNum><DisplayText>(Zdebiketal.,2009)</DisplayText><record><rec-number>1285</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1585990953">1285</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Zdebik,AnselmA.</author><author>Wangemann,Philine</author><author>Jentsch,ThomasJ.</author></authors></contributors><titles><title>PotassiumIonMovementintheInnerEar:InsightsfromGeneticDiseaseandMouseModels</title><secondary-title>Physiology</secondary-title></titles><periodical><full-title>Physiology</full-title></periodical><pages>307-316</pages><volume>24</volume><number>5</number><section>307</section><dates><year>2009</year></dates><isbn>1548-9213 1548-9221</isbn><urls></urls><electronic-resource-num>10.1152/physiol.00018.2009</electronic-resource-num></record></Cite></EndNote>(\o"Zdebik,2009#1285"Zdebiketal.,2009)血管纹因其内含有丰富的毛细血管而被如此命名，同时也是耳蜗血液循环系统的重要组成部分。耳蜗主要的血液供应来源是小脑下前动脉的分支之一螺旋蜗轴动脉。该动脉呈放射状延伸进入由血管纹和螺旋韧带，并形成耳蜗外侧壁组织主要的两大毛细血管系统ADDINEN.CITE<EndNote><Cite><Author>Shi</Author><Year>2011</Year><RecNum>1487</RecNum><DisplayText>(Shi,2011)</DisplayText><record><rec-number>1487</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1588125441">1487</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Shi,X.</author></authors></contributors><auth-address>OregonHearingResearchCenter(NRC04),DepartmentofOtolaryngology/Head&NeckSurgery,OregonHealth&ScienceUniversity,3181SWSamJacksonParkRoad,Portland,OR97239,USA.Shix@</auth-address><titles><title>Physiopathologyofthecochlearmicrocirculation</title><secondary-title>HearRes</secondary-title></titles><periodical><full-title>HearRes</full-title></periodical><pages>10-24</pages><volume>282</volume><number>1-2</number><edition>2011/08/31</edition><keywords><keyword>Animals</keyword><keyword>Cochlea/*bloodsupply</keyword><keyword>HearingDisorders/metabolism/pathology/*physiopathology</keyword><keyword>Humans</keyword><keyword>*Microcirculation</keyword><keyword>Microvessels/metabolism/pathology/*physiopathology</keyword><keyword>RegionalBloodFlow</keyword></keywords><dates><year>2011</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1878-5891(Electronic) 0378-5955(Linking)</isbn><accession-num>21875658</accession-num><urls><related-urls><url>/pubmed/21875658</url></related-urls></urls><custom2>PMC3608480</custom2><electronic-resource-num>10.1016/j.heares.2011.08.006</electronic-resource-num></record></Cite></EndNote>(\o"Shi,2011#1487"Shi,2011)。螺旋韧带中的毛细血管网由三部分组成，首先是位于螺旋韧带和前庭膜相接位置上方的小动脉系统；随之向下延伸的就是位于螺旋韧带组织内的真正的毛细血管网络，这些毛细血管大多都是垂直于蜗管延伸方向，即经向分布（REF_Ref65956047\h图1.8）。最后，螺旋韧带中丰富的毛细血管汇集到位于血管纹和基底膜相接位置附近的小静脉系统。血管纹中的毛细血管与螺旋韧带中的毛细血管不同的是，血管纹中的毛细血管形成了平行于蜗管延伸方向的多层网状结构，即横向分布（REF_Ref65956047\h图1.8）。蜗管底回血管纹的毛细血管网络更宽更复杂，随着血管纹往顶回延伸逐渐变窄变简单。除了空间上的差异性，血管纹中的毛细血管在发育过程中也有时间差异性。小鼠出生时，外侧壁仅有单层的毛细血管网络，从出生后第五天开始，从蜗管的底回到顶回逐渐形成血管纹和螺旋韧带两套毛细血管系统，大约在出生后八天血管纹和螺旋韧带的毛细血管系统各自发育完成ADDINEN.CITE<EndNote><Cite><Author>ToshinoriIwagaki</Author><Year>2000</Year><RecNum>1945</RecNum><DisplayText>(ToshinoriIwagaki,2000)</DisplayText><record><rec-number>1945</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1612870960">1945</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>ToshinoriIwagaki,ToruSuzuki,TsutomuNakashima</author></authors></contributors><titles><title>Developmentandregressionofcochlearbloodvesselsinfetalandnewbornmice</title><secondary-title>HearingResearch</secondary-title></titles><periodical><full-title>HearingResearch</full-title></periodical><dates><year>2000</year></dates><urls></urls></record></Cite></EndNote>(\o"ToshinoriIwagaki,2000#1945"ToshinoriIwagaki,2000)。图1.SEQ图1.\*ARABIC8耳蜗中阶外侧壁毛细血管网络扫描电镜图使用腐蚀铸造技术制备样品，并用扫描电镜观察耳蜗外侧壁的毛细血管网络。图中外侧螺旋韧带的毛细血管径向规则排布，内侧血管纹的毛细血管横向规则排布。ADDINEN.CITE<EndNote><Cite><Author>Carraro</Author><Year>2017</Year><RecNum>2007</RecNum><DisplayText>(Carraroetal.,2017)</DisplayText><record><rec-number>2007</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1614653493">2007</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Carraro,Mattia</author><author>Almishaal,Ali</author><author>Hillas,Elaine</author><author>Firpo,Matthew</author><author>Park,Albert</author><author>Harrison,RobertV.</author></authors></contributors><auth-address>InstituteofBiomaterialsandBiomedicalEngineering,UniversityofToronto,Toronto,ON,Canada. DepartmentofCommunicationSciencesandDisorders,UniversityofUtah,SaltLakeCity,UT,USA. DepartmentofSurgery,UniversityofUtah,SaltLakeCity,UT,USA. InstituteofBiomaterialsandBiomedicalEngineering,UniversityofToronto,Toronto,ON,Canada.rvh@sickkids.ca.</auth-address><titles><title>Cytomegalovirus(CMV)InfectionCausesDegenerationofCochlearVasculatureandHearingLossinaMouseModel</title><secondary-title>JournaloftheAssociationforResearchinOtolaryngology:JARO</secondary-title><alt-title>JAssocResOtolaryngol</alt-title></titles><alt-periodical><full-title>JAssocResOtolaryngol</full-title></alt-periodical><pages>263-273</pages><volume>18</volume><number>2</number><dates><year>2017</year></dates><isbn>1438-7573</isbn><accession-num>27995350</accession-num><urls><related-urls><url>/27995350</url><url>/pmc/articles/PMC5352614/pdf/10162_2016_Article_606.pdf</url></related-urls></urls><electronic-resource-num>10.1007/s10162-016-0606-4</electronic-resource-num><remote-database-name>PubMed</remote-database-name><language>eng</language></record></Cite></EndNote>(\o"Carraro,2017#2007"Carraroetal.,2017)螺旋韧带的毛细血管主要功能是提供并调节耳蜗外侧壁的血流ADDINEN.CITE<EndNote><Cite><Author>Spicer</Author><Year>2002</Year><RecNum>2119</RecNum><DisplayText>(SpicerandSchulte,2002)</DisplayText><record><rec-number>2119</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1616143737">2119</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Spicer,SamuelS.</author><author>Schulte,BradleyA.</author></authors></contributors><auth-address>DepartmentofPathologyandLaboratoryMedicine,MedicalUniversityofSouthCarolina,165AshleyAvenue,Charleston,SC29425,USA.schulteb@</auth-address><titles><title>Spiralligamentpathologyinquiet-agedgerbils</title><secondary-title>Hearingresearch</secondary-title><alt-title>HearRes</alt-title></titles><periodical><full-title>HearingResearch</full-title></periodical><alt-periodical><full-title>HearRes</full-title></alt-periodical><pages>172-185</pages><volume>172</volume><number>1-2</number><dates><year>2002</year></dates><isbn>0378-5955</isbn><accession-num>12361880</accession-num><urls><related-urls><url>/12361880</url></related-urls></urls><remote-database-name>PubMed</remote-database-name><language>eng</language></record></Cite></EndNote>(\o"Spicer,2002#2119"SpicerandSchulte,2002)，与之不同的是血管纹中的毛细血管有高度特化的血管上皮细胞和外周细胞ADDINEN.CITE<EndNote><Cite><Author>Shi</Author><Year>2011</Year><RecNum>1487</RecNum><DisplayText>(Shi,2011)</DisplayText><record><rec-number>1487</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"