韓建，何秋霞，韓利文，陳錫強(qiáng)，劉可春

山東省科學(xué)院生物研究所，山東省生物檢測(cè)技術(shù)工程實(shí)驗(yàn)室，山東省生物傳感器重點(diǎn)實(shí)驗(yàn)室，山東省科學(xué)院藥物篩選技術(shù)重點(diǎn)實(shí)驗(yàn)室，濟(jì)南250014

化學(xué)污染物對(duì)魚鰾的毒理學(xué)研究進(jìn)展

韓建，何秋霞，韓利文，陳錫強(qiáng)，劉可春*

山東省科學(xué)院生物研究所，山東省生物檢測(cè)技術(shù)工程實(shí)驗(yàn)室，山東省生物傳感器重點(diǎn)實(shí)驗(yàn)室，山東省科學(xué)院藥物篩選技術(shù)重點(diǎn)實(shí)驗(yàn)室，濟(jì)南250014

魚鰾(swimbladder)是幫助有鰾魚類完成呼吸、保持流體靜力、感覺(jué)聲音等生理活動(dòng)的重要功能器官之一?；瘜W(xué)污染物暴露能夠影響魚鰾的正常發(fā)育或充氣，對(duì)有鰾魚類的生存具有潛在威脅。本文首先對(duì)魚鰾功能、形態(tài)發(fā)育及分子機(jī)制進(jìn)行了介紹。其次對(duì)化學(xué)污染物導(dǎo)致的魚鰾發(fā)育異常或不充氣等毒性效應(yīng)進(jìn)行了總結(jié)，對(duì)特定污染物的潛在作用機(jī)制進(jìn)行了綜述。最后對(duì)魚鰾的環(huán)境/生態(tài)毒理學(xué)研究提出展望。

污染物；鰾；毒性評(píng)價(jià)

近年來(lái)，關(guān)于化學(xué)污染物導(dǎo)致有鰾魚類的魚鰾(swimbladder)發(fā)育異常、不充氣或缺失的科研報(bào)道逐漸增多。鰾作為功能器官有助于有鰾魚類完成呼吸、保持浮力、感覺(jué)聲音等生理學(xué)功能[1-2]。如果魚鰾因污染物暴露而無(wú)法正常發(fā)育或充氣，尤其是在早期發(fā)育階段受到影響，失去正常生理學(xué)功能，那么這些有鰾魚類的捕食、躲避、生長(zhǎng)、以及成魚階段的遷徙和生殖等行為均會(huì)受到嚴(yán)重影響，并且將最終導(dǎo)致其種群生存受到嚴(yán)重威脅[3]。在魚類分類中，骨鰾魚類(Ostariophysi)是真骨魚(Teleostei)中的第二大總目，包含5目、63科，近1 000屬，大約6 500種，約占全世界已知魚類種類的28%，約占淡水魚類種類的72%，分布在所有的大陸，其主要形態(tài)特征之一為具有鰾[4]?，F(xiàn)階段水環(huán)境污染狀況已然不容忽視。然而如此龐大的有鰾魚類種群正面臨化學(xué)污染物帶來(lái)的鰾毒性威脅。因此，評(píng)價(jià)化學(xué)污染物對(duì)魚鰾發(fā)育的毒性效應(yīng)，揭示潛在致毒機(jī)理，能夠?yàn)橛绪B魚類種群的生存保護(hù)和污染物的環(huán)境健康風(fēng)險(xiǎn)評(píng)價(jià)提供有力的科學(xué)依據(jù)。本文就魚鰾功能、形態(tài)發(fā)育和分子機(jī)制做簡(jiǎn)要介紹，對(duì)化學(xué)污染物等化學(xué)品的魚鰾毒性進(jìn)行了重點(diǎn)綜述，對(duì)魚鰾的環(huán)境/生態(tài)毒理學(xué)研究前景做了展望。

1 魚鰾功能、形態(tài)發(fā)育及分子機(jī)制(Function, morphological development and molecular mechanism of fish swimbladder)

1.1 魚鰾功能

魚鰾是一個(gè)充滿氣體的囊狀結(jié)構(gòu)，位于腸道的背部。對(duì)于當(dāng)前生存的大多數(shù)有鰾魚類，鰾是有助于保持流體靜力平衡、無(wú)呼吸功能的器官，而許多原始魚類和少數(shù)硬骨魚類可以通過(guò)鰾或肺進(jìn)行呼吸[1,5]。硬骨魚的肌肉、軟骨和硬骨等組織比其生存的水環(huán)境密度大，如果沒(méi)有浮力補(bǔ)償機(jī)制的話，其將在水中下沉，進(jìn)行捕食、遷徙和生殖等生命活動(dòng)的能量消耗將會(huì)變得巨大[3]。然而，魚類進(jìn)化出了諸多生理特點(diǎn)來(lái)增大浮力，比如具有充滿氣體的鰾，肌肉含水量高，合成低密度脂肪，以及減少骨量等[3]。鰾內(nèi)氣體可以降低魚體密度來(lái)抵消重力，通過(guò)控制氣體量可以讓魚體在一定水深范圍內(nèi)保持零浮力(neutral buoyancy)，有助于大多數(shù)魚類在水中以最低能耗來(lái)維持懸垂姿態(tài)，這對(duì)魚類生存是至關(guān)重要的[3,6]。除上述功能外，某些魚類的鰾還具有感覺(jué)聲音的功能。例如，除鼠鱚目外的所有骨鰾魚類顱側(cè)4或5塊椎骨形態(tài)發(fā)生明顯變化，形成韋伯氏器(Weberian ossicles)，連于鰾和內(nèi)耳之間來(lái)傳遞聲音[2,4]。

1.2 形態(tài)發(fā)育

不同種屬魚類鰾的形態(tài)結(jié)構(gòu)相似，可根據(jù)鰾與消化道之間有無(wú)連通結(jié)構(gòu)將現(xiàn)有有鰾魚類分為以下2個(gè)類別：成魚階段腸道與鰾之間有管狀結(jié)構(gòu)(pneumatic duct, 鰾管)相連通的魚類被稱為管鰾類(physostomes)，反之稱為閉鰾類(physoclists)[1]。關(guān)于鰾發(fā)育，研究較為透徹的魚類是斑馬魚(Danio rerio)。現(xiàn)以斑馬魚為例，來(lái)介紹鰾的基本發(fā)育過(guò)程。斑馬魚屬于管鰾類，其成魚階段具有連接腸道和鰾的鰾管，鰾管前部靠近頭的部分為前鰾(anterior chamber)，后部連接的為后鰾(posterior chamber)。斑馬魚魚鰾發(fā)育是先在胚胎發(fā)育階段形成后鰾，而后在幼魚階段形成前鰾。后鰾的發(fā)育可劃分為3個(gè)階段：出芽階段(budding phase, 36-65 hpf, hours post fertilization)，增長(zhǎng)/伸長(zhǎng)階段(growth/elongation phase, 65-96 hpf)，以及充氣階段(inflation phase, 96-120 hpf)[7]。出芽階段主要是指前腸部位(foregut)上皮細(xì)胞向背部突出形成鰾芽。增長(zhǎng)/伸長(zhǎng)階段主要是指鰾芽增長(zhǎng)并伸長(zhǎng)形成氣動(dòng)管(pneumatic duct)，末端發(fā)育形成后鰾，然后發(fā)育形成3個(gè)組織層，從內(nèi)到外依次為：(內(nèi))上皮層(epithelial layer)，間質(zhì)層(mesenchymal layer)和(外)間皮層(outer mesothelium)[7-8]。后鰾的充氣階段主要通過(guò)仔魚上浮到氣液面吞咽空氣(air gulping)來(lái)完成[7,9]。到18 dph(days post hatch)時(shí)，后鰾靠近顱側(cè)外突，形成聯(lián)通導(dǎo)管(ductus communicans)，導(dǎo)管末端形成前鰾芽，隨后前、后鰾均增長(zhǎng)、伸長(zhǎng)，血管、神經(jīng)和肌肉組織形成，到25～30 dph，整個(gè)鰾發(fā)育完成并呈現(xiàn)充氣狀態(tài)，其基本形態(tài)與成魚階段相同[7-8,10]。發(fā)育完成的鰾通過(guò)鰾管與消化道連通，其連接處形成了類似括約肌的結(jié)構(gòu)，前鰾腹側(cè)和后鰾兩側(cè)形成了較厚的肌肉帶，其他部位也形成了較薄的肌肉層；鰾的主動(dòng)、靜脈由前腸系膜動(dòng)脈的一枝延伸發(fā)育而來(lái)，并沿著鰾管分布至后鰾端口附近，而后逐級(jí)分支形成多個(gè)更細(xì)小的血管，動(dòng)、靜脈毛細(xì)血管遍布整個(gè)魚鰾，并形成血管網(wǎng)；鰾部的神經(jīng)纖維和終端分布情況與血管分布較為類似[10]。盡管后鰾第一次充氣使得仔魚浮力增加，但直到28～30 dph時(shí)幼魚魚鰾的血管、肌肉系統(tǒng)和神經(jīng)支配才發(fā)育完全，從而實(shí)現(xiàn)對(duì)鰾的自主控制[8]。斑馬魚早期生命階段發(fā)育快，體壁透明便于活體觀察，分子生物學(xué)背景和前期研究基礎(chǔ)較為充實(shí)[3]。因此，通過(guò)研究污染物對(duì)斑馬魚魚鰾的毒性效應(yīng)和致毒機(jī)理，有助于揭示污染物對(duì)有鰾魚類的毒性效應(yīng)和毒理學(xué)作用模式等。

1.3 分子機(jī)制

鰾的生長(zhǎng)發(fā)育受hedgehog(Hh)和Wnt通路調(diào)控，這2個(gè)信號(hào)通路在脊椎動(dòng)物發(fā)育調(diào)控中高度保守[7,11]。在鰾發(fā)育初期，Wnt/β-catenin信號(hào)通路參與調(diào)控由前腸內(nèi)胚層(foregut endoderm)向肝臟、胰腺和鰾的發(fā)育過(guò)程，敲降wnt2或wnt2bb均能夠?qū)е卖~鰾發(fā)育不全(hypoplasia)，這2個(gè)配體同時(shí)存在是鰾正常發(fā)育的必要條件[12]。通過(guò)對(duì)Wnt信號(hào)通路中的因子表達(dá)進(jìn)行分析，發(fā)現(xiàn)wnt5b表達(dá)于鰾間質(zhì)層細(xì)胞；fz2和fz7b這2個(gè)受體在間質(zhì)層和外間皮層均有表達(dá)；lef1和tcf3均在Wnt通路中既能起共激活因子的作用，又能作為Wnt信號(hào)的下游靶標(biāo)，前者表達(dá)于間質(zhì)層和外間皮層，而后者在上皮層、間質(zhì)層和外間皮層均有表達(dá)。通過(guò)抑制Wnt信號(hào)傳導(dǎo)，發(fā)現(xiàn)魚鰾發(fā)育和分化均受到抑制，其部分原因是各組織層的細(xì)胞增殖受阻和凋亡增加[13]。此外，還有研究證據(jù)表明，Wnt信號(hào)通路與hedgehog信號(hào)通路之間存在交互作用(cross-talk)，即Hh信號(hào)通路受Wnt信號(hào)通路調(diào)節(jié)，并與之形成負(fù)反饋調(diào)節(jié)[13-14]。

利用基因突變品系和基因敲降(morpholino knockdown)等分子生物學(xué)技術(shù)研究Hh信號(hào)通路在斑馬魚魚鰾早期發(fā)育階段中的調(diào)控作用，發(fā)現(xiàn)Sonic Hedgehog (Shha)是魚鰾上皮、間質(zhì)層細(xì)胞生長(zhǎng)和平滑肌細(xì)胞分化所必須的調(diào)控因子；Indian Hedgehog (Ihha)也是魚鰾上皮生長(zhǎng)和間質(zhì)層平滑肌細(xì)胞分化所必須的調(diào)控因子；抑制Hh信號(hào)通路，能夠?qū)е律掀ず烷g質(zhì)層的缺失，以及外間皮層組織的破壞；Hh信號(hào)通路是通過(guò)調(diào)節(jié)魚鰾3個(gè)組織層的細(xì)胞增殖來(lái)促進(jìn)其發(fā)育的[7]。然而，在鰾發(fā)育過(guò)程中Ihha基因與Shha基因的表達(dá)和生理功能是并行且互相獨(dú)立的[15]。實(shí)驗(yàn)證據(jù)同時(shí)表明，fibroblast growth factor 10a (FGF10a)表達(dá)于鰾的間質(zhì)層，fgf10a基因點(diǎn)突變后會(huì)導(dǎo)致魚鰾發(fā)育缺陷；表達(dá)于間質(zhì)層的fgf10a和Ptcs(Ihha基因受體)與表達(dá)于上皮部位的Ihha和fgfr2(fgf10a基因受體)構(gòu)成了相互依賴的反饋調(diào)控環(huán)，是魚鰾組織正常發(fā)育的重要調(diào)控環(huán)節(jié)[15]。另有研究報(bào)道，敲降pbx1 (pre-b-cell leukemia homeobox 1)轉(zhuǎn)錄因子的表達(dá)水平能夠?qū)е瞒B不充氣；機(jī)制研究結(jié)果暗示其可能在鰾發(fā)育后期起重要調(diào)控作用[16]。

2 魚鰾毒理學(xué)研究現(xiàn)狀(Toxicological research progress on fish swimbladder)

目前關(guān)于污染物暴露引起魚鰾毒性的科研報(bào)道越來(lái)越多，但大部分研究只是將魚鰾表型的改變作為評(píng)價(jià)發(fā)育毒性的諸多形態(tài)學(xué)指標(biāo)之一，少數(shù)研究則對(duì)魚鰾發(fā)育的組織形態(tài)學(xué)變化和潛在作用機(jī)制進(jìn)行了較為細(xì)致、全面的探討。因此，根據(jù)研究目的和深入程度不同，可將現(xiàn)有科研報(bào)道大致分為2類：一類是效應(yīng)研究，即在評(píng)價(jià)胚胎/仔魚發(fā)育毒性效應(yīng)時(shí)描述了后鰾形態(tài)變化，只觀察到表型為不充氣狀態(tài)；另一類是機(jī)制研究，即評(píng)價(jià)了特定污染物對(duì)魚鰾發(fā)育的毒性效應(yīng)和致毒機(jī)理。

2.1 效應(yīng)研究

無(wú)論是除草劑、二嗪農(nóng)、多菌靈、菊酯類等農(nóng)藥，還是抗生素類化合物，都能夠引起魚鰾異常。例如，研究酰胺類除草劑(甲草胺等)和農(nóng)藥表面活性劑(農(nóng)乳700等)對(duì)斑馬魚胚胎發(fā)育的毒性效應(yīng)，均發(fā)現(xiàn)游囊(即鰾)關(guān)閉現(xiàn)象，即后鰾表現(xiàn)為不充氣狀態(tài)[17-18]。二嗪農(nóng)(diazinon)暴露則能夠引起日本青鳉(medaka, Oryzias latipes)胚胎的孵化率降低，體長(zhǎng)變短，并伴有嚴(yán)重心包和卵黃囊水腫，以及鰾不充氣[19]。多菌靈暴露能引起斑馬魚胚胎發(fā)育畸形，包括后鰾缺失等[20]。研究芐氯菊酯和氯氰菊酯在單一或復(fù)合暴露條件下對(duì)日本青鳉胚胎及仔魚的毒性效應(yīng)，發(fā)現(xiàn)2種殺蟲劑在亞致死濃度下不論是單一還是復(fù)合暴露均能夠阻礙鰾的正常充氣[21-23]。雷帕霉素、氯霉素和磺胺嘧啶單一暴露均能引起斑馬魚胚胎發(fā)育畸形，主要特征有心包或卵黃囊水腫、脊柱彎曲、出血、凝血、尾部彎曲和后鰾缺失等[24-26]。

常見(jiàn)環(huán)境有機(jī)類污染物、化工原料等也能夠引起魚鰾不充氣或發(fā)育缺陷。例如，四溴雙酚A(TBBPA, 4 μmol·L-1)或雙酚AF (≥ 1.5 mg·L-1)暴露均能夠?qū)е掳唏R魚后鰾發(fā)育缺陷(不充氣)，幼魚出現(xiàn)心包水腫、卵黃囊水腫、軀體彎曲、死亡等現(xiàn)象[27-28]。雙酚A (≥ 500 μg·L-1)暴露能夠?qū)е掳唏R魚仔魚心包水腫、顱面部發(fā)育異常、后鰾不充氣和觸碰反應(yīng)遲鈍等[29]。此外，溴代阻燃劑六溴環(huán)十二烷(HBCD)和2,2',4,4'-四溴聯(lián)苯醚(BDE-47)均能夠引起斑馬魚仔后鰾發(fā)育或充氣異常[30-31]。經(jīng)苯并芘(B(a)P)或二惡英(TCDD)暴露后孵化的金頭鯛(seabream, Sparus aurata)，孵化率下降，伴有嚴(yán)重皮下水腫和組織壞死，其鰾的充氣受到阻礙[32]。另有研究發(fā)現(xiàn)，高氯酸鈉和氯化石蠟暴露均能引起斑馬魚胚胎的后鰾缺失[33-34]。以稀有鮈鯽(rare minnow, Gobiocypris rarus)為模型，研究氯化銨或?qū)β缺桨穼?duì)胚胎發(fā)育的影響，結(jié)果發(fā)現(xiàn)氯化銨和對(duì)氯苯胺均能影響鰾的正常發(fā)育充氣，導(dǎo)致自由游動(dòng)能力差等現(xiàn)象[35-36]。

重金屬暴露也能夠干擾魚鰾的正常發(fā)育或充氣。例如，銀離子(≥ 0.1 μmol·L-1)在較低暴露濃度下引起斑馬魚仔魚后鰾不充氣，從而影響了其游動(dòng)能力，進(jìn)而影響了其生存[37]。研究重金屬鎘和銅對(duì)雅羅魚(Leuciscus idus)及丁鱥魚(Tinca tinca)胚胎發(fā)育的影響，發(fā)現(xiàn)鎘或銅(≥ 100 μg·L-1)均能夠引起死亡率升高、發(fā)育遲緩、以及鰾異常等現(xiàn)象[38-39]。除了單一暴露，Yang等[40]還研究了鎘與氯氰菊酯在復(fù)合暴露條件下對(duì)斑馬魚胚胎發(fā)育的聯(lián)合毒性效應(yīng)，發(fā)現(xiàn)鎘(≥ 200 μg·L-1)增強(qiáng)了氯氰菊酯的毒性效應(yīng)，如仔魚身體彎曲、心包水腫、鰾不充氣、痙攣和氧化應(yīng)激等。

除上述報(bào)道外，相關(guān)科研人員還研究了常用水產(chǎn)消毒劑(亞甲基藍(lán)、雙氧水、吖啶黃和氯胺T)或溫度(26 ℃和28 ℃)對(duì)神仙魚(angelfish, Pterophyllum scalare L.)鰾充氣的影響，結(jié)果顯示除了氯胺-T外，其余消毒劑均能夠顯著引起鰾不充氣；26 ℃水溫能夠引起8%的個(gè)體鰾不充氣，但28 ℃水溫下的個(gè)體鰾形態(tài)均正常[41-42]。

2.2 機(jī)制研究

化學(xué)污染物對(duì)魚鰾毒性致毒機(jī)理的研究報(bào)道非常少?，F(xiàn)有研究大多是以斑馬魚為模式動(dòng)物，集中于評(píng)價(jià)典型持久性有機(jī)污染物對(duì)胚胎/卵黃囊仔魚期后鰾發(fā)育的影響。例如，斑馬魚芳香烴受體(zebrafish aryl hydrocarbon receptor 2, zfAHR2)能夠介導(dǎo)2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)產(chǎn)生心包、卵黃囊和腦膜水腫，以及下頜發(fā)育短小和后鰾不充氣等發(fā)育毒性[43]。另有研究表明，TCDD在0～72 hpf內(nèi)暴露對(duì)斑馬魚后鰾的發(fā)育形態(tài)學(xué)變化并無(wú)顯著性影響，但暴露個(gè)體在120 hpf時(shí)均無(wú)法形成正常的后鰾，說(shuō)明TCDD引起鰾毒性的敏感暴露期是胚胎發(fā)育的前72 hpf；作者還推測(cè)TCDD引起仔魚心力衰竭，從而導(dǎo)致血液循環(huán)系統(tǒng)故障，繼而導(dǎo)致了后鰾發(fā)育異常[44]。3,3',4,4',5-五氯聯(lián)苯(PCB126)同樣能夠通過(guò)zfAHR2介導(dǎo)產(chǎn)生鰾毒性，導(dǎo)致后鰾鰾壁變薄，組織細(xì)胞發(fā)育異常，從而阻礙了后鰾的發(fā)育和充氣，同時(shí)結(jié)果顯示引起心包水腫的PCB126濃度(5 nmol·L-1)要高于引起鰾異常的濃度(2 nmol·L-1)[45]。三(2,3-二溴丙基)異氰脲酸酯(tris(2,3-dibromopropyl) isocyanurate, TBC, 2.5 μg·L-1)暴露能夠?qū)е掳唏R魚后鰾充氣異常，但未引起水腫之類的毒性效應(yīng)，暴露敏感窗口期篩查結(jié)果表明敏感暴露期為72～96 hpf，這與后鰾開(kāi)始充氣的時(shí)間相吻合；與發(fā)育調(diào)控相關(guān)基因表達(dá)水平?jīng)]有顯著變化，如Hedgehog信號(hào)通路中的shha和ihha基因，以及growth hormone/prolactin (GH/PRL)超家族中的prolactin基因和somatolactin基因，這表明后鰾的發(fā)育調(diào)控并未受到顯著影響；超微結(jié)構(gòu)觀察結(jié)果顯示鰾組織細(xì)胞內(nèi)囊泡萎縮和線粒體損傷；并且作者建議應(yīng)當(dāng)將鰾毒性評(píng)價(jià)納入魚類胚胎毒性測(cè)試方案中，作為必要的常規(guī)檢測(cè)指標(biāo)[46]。較高濃度的全氟辛烷磺酸(PFOS, ≥ 16 μmol·L-1)通過(guò)干擾多個(gè)胚胎發(fā)育相關(guān)分子調(diào)控途徑來(lái)影響后鰾和腸道發(fā)育，致使后鰾不充氣，組織病理學(xué)結(jié)果顯示出一定程度的病變；暴露產(chǎn)生的活性氧簇(reactive oxygen species, ROS)引起了II相酶(phase II detoxification enzymes)和nuclear factor erythroid 2 related factor (nrf2)信號(hào)通路中某些基因表達(dá)變化，從而揭示了氧化應(yīng)激(oxidative stress)很可能在PFOS暴露導(dǎo)致的發(fā)育毒性中起重要作用[47]。另一研究對(duì)PFOS暴露敏感期進(jìn)行了篩查，發(fā)現(xiàn)受影響的主要發(fā)育時(shí)期是后鰾充氣階段，PFOS (≥ 3.07 mg·L-1)暴露持續(xù)3 d或以上導(dǎo)致后鰾大小、體長(zhǎng)和運(yùn)動(dòng)速度的顯著下降[48]。

目前關(guān)于前鰾發(fā)育毒性的研究也非常少。為了驗(yàn)證甲狀腺受化學(xué)污染物干擾后，能夠引起鰾發(fā)育異常，研究人員分別以斑馬魚和黑頭呆魚(fathead minnow, Pimephales promelas)為模型，研究了甲狀腺過(guò)氧化酶抑制劑2-mercaptobenzothiazole (MBT)對(duì)甲狀腺激素水平和鰾發(fā)育的影響，MBT暴露并沒(méi)有對(duì)后鰾發(fā)育造成影響，而單純導(dǎo)致前鰾發(fā)育毒性效應(yīng)，間接說(shuō)明了污染物干擾甲狀腺激素調(diào)控系統(tǒng)會(huì)最終導(dǎo)致前鰾發(fā)育異常[49-50]。

3 總結(jié)與展望(Summary and perspective)

魚鰾是有鰾魚類的重要功能器官。關(guān)于魚鰾毒理學(xué)的科研報(bào)道越來(lái)越多，說(shuō)明科研人員對(duì)化學(xué)品暴露導(dǎo)致魚鰾毒性的關(guān)注和重視程度越來(lái)越高。前述研究結(jié)果表明，不論是農(nóng)藥、水產(chǎn)用藥、抗生素，還是典型有機(jī)類污染物、重金屬等，均對(duì)魚鰾的正常發(fā)育或充氣具有潛在威脅。這說(shuō)明水環(huán)境中存在諸多能夠引起魚鰾異常的危險(xiǎn)因素。然而，評(píng)價(jià)化學(xué)污染物等引起魚鰾異常的毒理學(xué)研究尚處于起步階段，仍然存在諸多問(wèn)題亟需解決。因此，當(dāng)前急需充分挖掘和利用現(xiàn)有魚類動(dòng)物模型，來(lái)積極開(kāi)展魚鰾毒理學(xué)研究，并著重解決以下幾個(gè)方面的問(wèn)題：

⑴大部分實(shí)驗(yàn)暴露濃度較高，導(dǎo)致大多數(shù)實(shí)驗(yàn)中都伴隨有水腫、畸形等嚴(yán)重的表型變化。因此，開(kāi)展較低劑量下魚鰾發(fā)育毒性的研究，同時(shí)需要明確魚鰾毒性在諸多亞致死毒性效應(yīng)指標(biāo)中所處的位置。

⑵當(dāng)前，絕大多數(shù)研究只對(duì)污染物暴露引起的后鰾發(fā)育表型和病理變化做了檢測(cè)，缺乏對(duì)后鰾發(fā)育以及整個(gè)魚鰾功能調(diào)節(jié)等方面的毒理學(xué)研究。

⑶不同化學(xué)品的致毒機(jī)制可能有所不同，但現(xiàn)有鰾毒性的致毒機(jī)制研究都比較模糊。因此，需要針對(duì)不同污染物的毒性特點(diǎn)做深入研究。

⑷實(shí)際水環(huán)境污染狀況比較復(fù)雜，多種污染物同時(shí)存在，復(fù)合暴露毒性評(píng)價(jià)已成為當(dāng)前環(huán)境/生態(tài)毒理學(xué)研究的熱點(diǎn)之一[51]。因此，有必要在研究單一暴露毒性的同時(shí)開(kāi)展復(fù)合暴露條件下的魚鰾毒理學(xué)評(píng)價(jià)工作。

致謝：感謝華中農(nóng)業(yè)大學(xué)水產(chǎn)學(xué)院(武漢)劉春生研究員在文章修改中給予的幫助。

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Review on Toxicology of Chemical Pollutants on Fish Swimbladder

Han Jian, He Qiuxia, Han Liwen, Chen Xiqiang, Liu Kechun*

Biology Institute of Shandong Academy of Sciences, Shandong Provincial Engineering Laboratory for Biological Testing Technology, Key Laboaratory for Biosensor of Shandong Province, Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, Jinan 250014, China

Received 25 July 2016 accepted 29 September 2016

Swimbladder is one of the most essential organs for the fish with such a gas chamber, and plays a key role in performing respiration, keeping hydrostatics and sensing sound, etc. Exposure to chemical contaminants could affect development and inflation of fish swimbladder, and thus might lead to a potential threat to fish with swimbladder. In this review, firstly, the function, morphological development and molecular mechanisms of fish swimbladder were introduced. Secondly, the reports on abnormal development of swimbladder and its non-inflation caused by exposure to chemical pollutants were summarized, and the potential mechanisms of action were reviewed. Finally, the perspectives on environmental toxicology or ecotoxicology of fish swimbladder were proposed.

contaminants; swimbladder; toxicity evaluation

山東省科學(xué)院青年基金項(xiàng)目(2015QN012)；山東省自主創(chuàng)新及成果轉(zhuǎn)化專項(xiàng)(2014ZZCX02105)；山東省自然科學(xué)基金三院聯(lián)合基金項(xiàng)目(ZR2015YL013)

韓建(1983-)，男，博士，助理研究員，研究方向?yàn)榄h(huán)境/生態(tài)毒理學(xué)和藥物篩選，E-mail: hanjian251314@163.com；

*通訊作者(Corresponding author)， E-mail: hliukch@sdas.org

10.7524/AJE.1673-5897.20160725001

2016-07-25 錄用日期：2016-09-29

1673-5897(2016)6-037-07

X171.5

A

劉可春(1964-)，男，博士，研究員，研究方向?yàn)槎纠韺W(xué)和藥物篩選。

韓建, 何秋霞, 韓利文, 等. 化學(xué)污染物對(duì)魚鰾的毒理學(xué)研究進(jìn)展[J]. 生態(tài)毒理學(xué)報(bào)，2016, 11(6): 37-43

Han J, He Q X, Han L W, et al. Review on toxicology of chemical pollutants on fish swimbladder [J]. Asian Journal of Ecotoxicology, 2016, 11(6): 37-43 (in Chinese)