养殖半滑舌鳎常见疾病的病理学观察与感染微生态分析
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摘要
半滑舌鳎（Cynoglossus semilaevis Günther）是原产我国近海的优良海水鱼类品种，也是继牙鲆和大菱鲆之后，其养殖形成产业规模的又一鲆鲽鱼类。本论文以养殖的半滑舌鳎为研究对象，采用现场调查、石蜡切片、细菌分离培养、PCR-DGGE和Roche454平台高通量测序等技术方法，分别进行了初步的流行病调查，代表性的疾病病理学和感染微生态的研究，以期充实和丰富鲆鲽鱼类疾病研究的资料，并为半滑舌鳎疾病高效防控技术体系的构建奠定工作基础。论文的主要研究结果如下：
1.养殖半滑舌鳎主要的流行病类型
论文流行病调查的范围集中于山东半岛，调查的方式以现场采样和来样送检为主。通过调查，发现在我国北方半滑舌鳎的主要养殖区，疾病逐渐成为养殖生产中经常面对的问题，对产业的平稳发展已经构成了威胁。调查同时发现，烂鳍烂尾症、皮肤溃疡症、皮下脓肿病、腹水病和肠炎病是半滑舌鳎养殖过程比较常见的几种疾病，这些疾病都具有非常明显的临床病变特征，在生产中比较容易识别。在所采集的半滑舌鳎疾病样品中，没有发现寄生虫性疾病和病毒性疾病。
2.养殖半滑舌鳎代表性疾病的病理学研究
选取皮肤溃疡症和腹水病这两种有代表性的疾病进行了组织病理学的观察。观察结果显示，感染皮肤溃疡的半滑舌鳎除体表出现明显病灶外，全身主要的组织器官都发生了不同程度的病理变化。如溃疡病灶处肌纤维发生了严重的固缩，并有局灶性溃烂；鳃小叶局部组织水肿，毛细血管扩张并充血；鳍组织表现了真皮层充血的病理变化；眼部视网膜的內颗粒层和外网状层发生剥离；肝胰脏和肾脏发生了严重的组织变性、坏死和溃烂等病理变化；脾脏血红细胞大量坏死和沉积；心脏出现了心肌组织的大面积坏死和血细胞、淋巴细胞浸润现象；消化道的粘膜层和粘膜固有层分离，并有局灶性的组织增生和溃烂现象。而感染腹水病的半滑舌鳎全身各个组织器官也出现了不同程度的病变，但整体病变程度相对皮肤溃疡症病鱼较轻。腹水病病鱼主要组织器官的病理表现为：皮肤真皮层出现大量点状淤血；鳃小叶上皮细胞水肿和柱状细胞组织增生；心肌组织局灶性断裂；肝胰脏也出现局灶性组织坏死和溃烂；肾小球与肾间质发生了组织融合；胆囊壁形成血栓，并发生明显的结缔组织增生；脑组织中可以发现空泡变性和颗粒变性的神经细胞；胃的粘膜固有层出现局灶性组织坏死，而肠道的组织病变和胃基本一样。病理学的分析结果说明，多器官的病变使器官功能衰竭，正常的生理代谢逐渐下降并消失，这可能是皮肤溃疡症和腹水病病鱼发生死亡的最终原因。
3.池塘养殖半滑舌鳎的微生态研究
从池塘养殖的健康半滑舌鳎中随机挑选了3条样本鱼，用微生物分离培养、PCR-DGGE和Roche454平台的高通量测序技术分别对它们体内各个组织中和环境中菌群的相关性进行了分析。研究结果发现，传统的微生物分离培养方法仅能从样品鱼的肠道、水样和底泥中分离出细菌，这些细菌都是弧菌属细菌。以这些细菌为依据，不能很好的解析各样品之间的菌群相关性。PCR-DGGE技术可以定性解析半滑舌鳎组织、水样和底泥中菌群的相关性，通过对电泳条带的切胶回收和测序，也能较好的体现各个样品的菌群多样性，但平行样之间的结果分析存在一定的的误差。通过对高通量测序数据的分析，证实池塘养殖的半滑舌鳎各个组织中菌群构成非常相似，并且与所投喂饵料中菌群结构存在一定的相关性，而几乎不受养殖水体和池塘底泥中菌群的影响。
4.工厂化养殖半滑舌鳎疾病发生的感染微生态研究
采用上述3种实验方法，同时对两家工厂化养殖厂感染皮肤溃疡症和腹水病的半滑舌鳎病鱼进行了感染微生态的分析。病鱼样品为皮肤溃疡症和腹水病病鱼各3条，同一养殖系统中未发病的正常鱼各1条。研究结果表明，传统的培养方法仅能从少部分病鱼的病灶和肠道中分离出细菌，这些细菌分别归属弧菌属、交替单胞菌属、假单胞菌属、希瓦氏菌属等不同菌属，因此仍无法解析各样品间菌群构成的相关性。PCR-DGGE实验结果证实皮肤溃疡症病鱼和腹水病病鱼体内不同组织中的优势菌群的构成具有一定的相似性，与正常鱼相比存在较为明显的差异性。PCR-DGGE的实验结果同时证实工厂化养殖半滑舌鳎肠道菌群的构成似乎与水体和饵料中的菌群构成不太相关。采用高通量测序技术对其中4条样本鱼及水样和饵料样本进行测序分析，结果表明样本鱼各个组织中优势菌株的种类构成非常相似，并且与水样和饵料中的菌群相关性不明显，但其丰度在发病前后发生了显著变化，即优势菌株的生态位在疾病发生的前后发生了转变。通过高通量测序获得的半滑舌鳎各组织中优势细菌的16S rRNA序列大部分在NCBI数据库中没有可供比对的已知菌种序列。
通过以上研究，本论文引申了两点推测。一是在本论文的研究案例中，所有样本鱼组织中的优势菌种组成几乎是相同的，因此人工养殖的半滑舌鳎体内可能存在特异的共生菌群，这一菌群可能在苗种培育阶段就已定植半滑舌鳎体内，且不受养殖模式、养殖环境、鱼体健康状态的影响而发生改变，并对外源菌具有排他性。二是在工厂化养殖系统中，各个组织器官中这一菌群的优势菌株在鱼体全身微生态系统中发生了明显的生态位改变，这有可能是疾病发生的直接诱因之一。
Half-smooth tongue sole (Cynoglossus semilaevis Günther) is one marine fishspecies native to northern China offshore areas. And also, it is another flatfish whichits farming forming industrial scale after Japanese flounder (Paralichthys olivaceus)and turbot (Scophthalmus maximus) in China. In this paper, epizootic investigationhas been performed and typical disease samples are selected for histopathology andinfectious microecology research in cultured half-smooth tongue sole by usingon-site investigations, paraffin section technique, microorganism cultivating,PCR-DGGE and PTS-454(high-through sequencing technique based on Roche454platform) methods respectively. The results of these studies will enrich the data offlatfish diseases research, and provide the fundamental works for constructinghalf-smooth tongue sole disease control and prevention techniques system. All theresults of this paper are as follows:
1. The common diseases in cultured half-smooth tongue sole
All the diseased fishes for epizootic investigation in this paper are sampled infarms or derived from arrived samples for inspection from Shandong Peninsula, China.The results show that diseases occurred frequently and pose a threat to the sustainabledevelopment of half-smooth tongue sole farming industry. The investigation also findthat fin and tail rot, skin ulceration, subcutaneous abscess, ascites and enteritis werethe most common diseases in cultured half-smooth tongue sole in China. Thesediseases have conspicuous clinical epidemiologic characteristics and are easilyrecognizable in farming. There are no viral and parasitic disease fish in our collection samples.
2. Histopathology of cultured half-smooth tongue sole typical diseases
As the typical diseases, the fish associated with skin ulcer and ascites symptomare respectively chosen for histopathology analysis. The results reveal that mostorgans of skin ulcer fish exhibit varying organ lesion beside the ulceration on the body.The major organs pathological changes of diseased fish include muscle fiberspyknosis and focal ulceration, branchial lamella oedema and capillaries dilation withcongestion, red blood cells infiltration in the derma of the fin, the detachment of innernuclear layer and outer plexiform layer in the retina, tissues necrosis and ulcer in thehepatopancreas and kidney, dead red blood cells accumulation in the spleen, necrosisof myocardium and hemocyte and lymphocyte infiltration in the heart, detachment ofmucosal epithelium and lamina propria and focal epithelial tissues hyperplasia andulceration in gastrointestinal tract. The diseased fish associated with ascites also showdifferent pathological changes in most organs. Comparing to skin ulcer disease, thesefish organs lesions are relatively lesser degree. The major damage of organs indiseased fish with ascites symptom are: spot congestion in dermis, epithelium oedemaand cylindrical cell hyperplasia in branchial lamella, myocardium focal fracture,tissue focal necrosis in hepatopancreas, the fusion of glomerulu and renal interstitium,thrombosis and connective tissue hyperplasia of gallbladder wall, neural cellsvacuolar and granular degeneration existence in brain, lamina propria focal necrosis instomach and intestine. Surmising from the results, multiple organ tissues damage andmetabolic dysfunction or loss, this may be the ultimate cause of death in diseased fish.
3. Microecology characteristics of cultured half-smooth tongue sole in outdoorpond
Three healthy half-smooth tongue sole are randomly selected form the outdoorculture pond for correlation analysis of microflora in different fish organs, water, pondsediment and pellet feed using microorganism cultivating, PCR-DGGE and PTS-454(high-through sequencing technique based on Roche454platform) methods. The studies find that only vibrios can be isolated form fish intestine, water and pondsediment using traditional microorganism cultivating method. But the results ofbacteria isolation are not enough to support the correlativity analysis of microflora inthe samples. Using PCR-DGGE technique, the correlation of microbial communitiesin fish organs, water and pond sediment can be qualitatively analyzed. And microbialdiversity in these samples is also analyzed through the electrophoretic bandsrecovering and sequencing. But there are some deviations which can not be avoided inparallel experiment. According to the analysis of PTS-454results, we can confirm thatthe microbial community structure in half-smooth tongue sole different organs is verysimilar. It is also relevant to the microflora in pellet feed for feeding, while almostindependent from the microflora in water and pond sediment.
4. Infectious microecology characteristics of diseased half-smooth tongue sole inindoor farming system
The infectious characteristics of diseased half-smooth tongue sole respectivelyassociated with skin uler and ascites are also analyzed using the three aforementionedmethods. Three diseased fishes associated with skin ulceration symptom and onenormal fish in the same farming system as samples are derived from one indoor farm,and three diseased fishes associate with ascites and one normal fish in the samefarming system from another indoor farm. Bacteria can be isolated only from portionsof diseased fish focal ulceration and intestine. These becteria belong to Vibrios,Alteromonas, Pseudomonas, Shewanella, etc. It is still difficult to analyze thecorrelation of microbial community structure in the samples basing on these bacteriaisolation. However, the similarity between the microflora in different organs ofdiseased fish but different from normal fish organs are confirmed by PCR-DGGEmethod. The results also reveal the limited relationship of microflora betweenhalf-smooth tongue sole intenstine, water and pellet feed in indoor farming system.The water, pellet feed and four fishes are also studied the microbial communitystructure by PTS-454method. The results show that predominant strains in all fishorgans are similar and different from those in water and pellet feed. But the abundance of different predominant strains changes noticeably during the diseaseoccurrence. This means that the microecology niche of predominant strains reverseafter disease occurrence. Most of bacterial16S rRNA sequences obtaining byPTS-454can not find the similar data in NCBI GenBank.
Summarizing these results, two suppositions are brought forward. First, in thecases of this paper, the predominant bacteria in all fish samples are almost the same.Obviously, there may be symbiotic microflora in cultured half-smooth tongue solebody. These bacteria are exclusivity and regardless of farming system, environmentand fish health changes. It can be colonization during the larval fish rearing stage.Second, in the indoor farming system, the microecology niche of these bacteriachanged in the fish body, which may be the direct cause of disease occurrence.
1.养殖半滑舌鳎主要的流行病类型
论文流行病调查的范围集中于山东半岛，调查的方式以现场采样和来样送检为主。通过调查，发现在我国北方半滑舌鳎的主要养殖区，疾病逐渐成为养殖生产中经常面对的问题，对产业的平稳发展已经构成了威胁。调查同时发现，烂鳍烂尾症、皮肤溃疡症、皮下脓肿病、腹水病和肠炎病是半滑舌鳎养殖过程比较常见的几种疾病，这些疾病都具有非常明显的临床病变特征，在生产中比较容易识别。在所采集的半滑舌鳎疾病样品中，没有发现寄生虫性疾病和病毒性疾病。
2.养殖半滑舌鳎代表性疾病的病理学研究
选取皮肤溃疡症和腹水病这两种有代表性的疾病进行了组织病理学的观察。观察结果显示，感染皮肤溃疡的半滑舌鳎除体表出现明显病灶外，全身主要的组织器官都发生了不同程度的病理变化。如溃疡病灶处肌纤维发生了严重的固缩，并有局灶性溃烂；鳃小叶局部组织水肿，毛细血管扩张并充血；鳍组织表现了真皮层充血的病理变化；眼部视网膜的內颗粒层和外网状层发生剥离；肝胰脏和肾脏发生了严重的组织变性、坏死和溃烂等病理变化；脾脏血红细胞大量坏死和沉积；心脏出现了心肌组织的大面积坏死和血细胞、淋巴细胞浸润现象；消化道的粘膜层和粘膜固有层分离，并有局灶性的组织增生和溃烂现象。而感染腹水病的半滑舌鳎全身各个组织器官也出现了不同程度的病变，但整体病变程度相对皮肤溃疡症病鱼较轻。腹水病病鱼主要组织器官的病理表现为：皮肤真皮层出现大量点状淤血；鳃小叶上皮细胞水肿和柱状细胞组织增生；心肌组织局灶性断裂；肝胰脏也出现局灶性组织坏死和溃烂；肾小球与肾间质发生了组织融合；胆囊壁形成血栓，并发生明显的结缔组织增生；脑组织中可以发现空泡变性和颗粒变性的神经细胞；胃的粘膜固有层出现局灶性组织坏死，而肠道的组织病变和胃基本一样。病理学的分析结果说明，多器官的病变使器官功能衰竭，正常的生理代谢逐渐下降并消失，这可能是皮肤溃疡症和腹水病病鱼发生死亡的最终原因。
3.池塘养殖半滑舌鳎的微生态研究
从池塘养殖的健康半滑舌鳎中随机挑选了3条样本鱼，用微生物分离培养、PCR-DGGE和Roche454平台的高通量测序技术分别对它们体内各个组织中和环境中菌群的相关性进行了分析。研究结果发现，传统的微生物分离培养方法仅能从样品鱼的肠道、水样和底泥中分离出细菌，这些细菌都是弧菌属细菌。以这些细菌为依据，不能很好的解析各样品之间的菌群相关性。PCR-DGGE技术可以定性解析半滑舌鳎组织、水样和底泥中菌群的相关性，通过对电泳条带的切胶回收和测序，也能较好的体现各个样品的菌群多样性，但平行样之间的结果分析存在一定的的误差。通过对高通量测序数据的分析，证实池塘养殖的半滑舌鳎各个组织中菌群构成非常相似，并且与所投喂饵料中菌群结构存在一定的相关性，而几乎不受养殖水体和池塘底泥中菌群的影响。
4.工厂化养殖半滑舌鳎疾病发生的感染微生态研究
采用上述3种实验方法，同时对两家工厂化养殖厂感染皮肤溃疡症和腹水病的半滑舌鳎病鱼进行了感染微生态的分析。病鱼样品为皮肤溃疡症和腹水病病鱼各3条，同一养殖系统中未发病的正常鱼各1条。研究结果表明，传统的培养方法仅能从少部分病鱼的病灶和肠道中分离出细菌，这些细菌分别归属弧菌属、交替单胞菌属、假单胞菌属、希瓦氏菌属等不同菌属，因此仍无法解析各样品间菌群构成的相关性。PCR-DGGE实验结果证实皮肤溃疡症病鱼和腹水病病鱼体内不同组织中的优势菌群的构成具有一定的相似性，与正常鱼相比存在较为明显的差异性。PCR-DGGE的实验结果同时证实工厂化养殖半滑舌鳎肠道菌群的构成似乎与水体和饵料中的菌群构成不太相关。采用高通量测序技术对其中4条样本鱼及水样和饵料样本进行测序分析，结果表明样本鱼各个组织中优势菌株的种类构成非常相似，并且与水样和饵料中的菌群相关性不明显，但其丰度在发病前后发生了显著变化，即优势菌株的生态位在疾病发生的前后发生了转变。通过高通量测序获得的半滑舌鳎各组织中优势细菌的16S rRNA序列大部分在NCBI数据库中没有可供比对的已知菌种序列。
通过以上研究，本论文引申了两点推测。一是在本论文的研究案例中，所有样本鱼组织中的优势菌种组成几乎是相同的，因此人工养殖的半滑舌鳎体内可能存在特异的共生菌群，这一菌群可能在苗种培育阶段就已定植半滑舌鳎体内，且不受养殖模式、养殖环境、鱼体健康状态的影响而发生改变，并对外源菌具有排他性。二是在工厂化养殖系统中，各个组织器官中这一菌群的优势菌株在鱼体全身微生态系统中发生了明显的生态位改变，这有可能是疾病发生的直接诱因之一。
Half-smooth tongue sole (Cynoglossus semilaevis Günther) is one marine fishspecies native to northern China offshore areas. And also, it is another flatfish whichits farming forming industrial scale after Japanese flounder (Paralichthys olivaceus)and turbot (Scophthalmus maximus) in China. In this paper, epizootic investigationhas been performed and typical disease samples are selected for histopathology andinfectious microecology research in cultured half-smooth tongue sole by usingon-site investigations, paraffin section technique, microorganism cultivating,PCR-DGGE and PTS-454(high-through sequencing technique based on Roche454platform) methods respectively. The results of these studies will enrich the data offlatfish diseases research, and provide the fundamental works for constructinghalf-smooth tongue sole disease control and prevention techniques system. All theresults of this paper are as follows:
1. The common diseases in cultured half-smooth tongue sole
All the diseased fishes for epizootic investigation in this paper are sampled infarms or derived from arrived samples for inspection from Shandong Peninsula, China.The results show that diseases occurred frequently and pose a threat to the sustainabledevelopment of half-smooth tongue sole farming industry. The investigation also findthat fin and tail rot, skin ulceration, subcutaneous abscess, ascites and enteritis werethe most common diseases in cultured half-smooth tongue sole in China. Thesediseases have conspicuous clinical epidemiologic characteristics and are easilyrecognizable in farming. There are no viral and parasitic disease fish in our collection samples.
2. Histopathology of cultured half-smooth tongue sole typical diseases
As the typical diseases, the fish associated with skin ulcer and ascites symptomare respectively chosen for histopathology analysis. The results reveal that mostorgans of skin ulcer fish exhibit varying organ lesion beside the ulceration on the body.The major organs pathological changes of diseased fish include muscle fiberspyknosis and focal ulceration, branchial lamella oedema and capillaries dilation withcongestion, red blood cells infiltration in the derma of the fin, the detachment of innernuclear layer and outer plexiform layer in the retina, tissues necrosis and ulcer in thehepatopancreas and kidney, dead red blood cells accumulation in the spleen, necrosisof myocardium and hemocyte and lymphocyte infiltration in the heart, detachment ofmucosal epithelium and lamina propria and focal epithelial tissues hyperplasia andulceration in gastrointestinal tract. The diseased fish associated with ascites also showdifferent pathological changes in most organs. Comparing to skin ulcer disease, thesefish organs lesions are relatively lesser degree. The major damage of organs indiseased fish with ascites symptom are: spot congestion in dermis, epithelium oedemaand cylindrical cell hyperplasia in branchial lamella, myocardium focal fracture,tissue focal necrosis in hepatopancreas, the fusion of glomerulu and renal interstitium,thrombosis and connective tissue hyperplasia of gallbladder wall, neural cellsvacuolar and granular degeneration existence in brain, lamina propria focal necrosis instomach and intestine. Surmising from the results, multiple organ tissues damage andmetabolic dysfunction or loss, this may be the ultimate cause of death in diseased fish.
3. Microecology characteristics of cultured half-smooth tongue sole in outdoorpond
Three healthy half-smooth tongue sole are randomly selected form the outdoorculture pond for correlation analysis of microflora in different fish organs, water, pondsediment and pellet feed using microorganism cultivating, PCR-DGGE and PTS-454(high-through sequencing technique based on Roche454platform) methods. The studies find that only vibrios can be isolated form fish intestine, water and pondsediment using traditional microorganism cultivating method. But the results ofbacteria isolation are not enough to support the correlativity analysis of microflora inthe samples. Using PCR-DGGE technique, the correlation of microbial communitiesin fish organs, water and pond sediment can be qualitatively analyzed. And microbialdiversity in these samples is also analyzed through the electrophoretic bandsrecovering and sequencing. But there are some deviations which can not be avoided inparallel experiment. According to the analysis of PTS-454results, we can confirm thatthe microbial community structure in half-smooth tongue sole different organs is verysimilar. It is also relevant to the microflora in pellet feed for feeding, while almostindependent from the microflora in water and pond sediment.
4. Infectious microecology characteristics of diseased half-smooth tongue sole inindoor farming system
The infectious characteristics of diseased half-smooth tongue sole respectivelyassociated with skin uler and ascites are also analyzed using the three aforementionedmethods. Three diseased fishes associated with skin ulceration symptom and onenormal fish in the same farming system as samples are derived from one indoor farm,and three diseased fishes associate with ascites and one normal fish in the samefarming system from another indoor farm. Bacteria can be isolated only from portionsof diseased fish focal ulceration and intestine. These becteria belong to Vibrios,Alteromonas, Pseudomonas, Shewanella, etc. It is still difficult to analyze thecorrelation of microbial community structure in the samples basing on these bacteriaisolation. However, the similarity between the microflora in different organs ofdiseased fish but different from normal fish organs are confirmed by PCR-DGGEmethod. The results also reveal the limited relationship of microflora betweenhalf-smooth tongue sole intenstine, water and pellet feed in indoor farming system.The water, pellet feed and four fishes are also studied the microbial communitystructure by PTS-454method. The results show that predominant strains in all fishorgans are similar and different from those in water and pellet feed. But the abundance of different predominant strains changes noticeably during the diseaseoccurrence. This means that the microecology niche of predominant strains reverseafter disease occurrence. Most of bacterial16S rRNA sequences obtaining byPTS-454can not find the similar data in NCBI GenBank.
Summarizing these results, two suppositions are brought forward. First, in thecases of this paper, the predominant bacteria in all fish samples are almost the same.Obviously, there may be symbiotic microflora in cultured half-smooth tongue solebody. These bacteria are exclusivity and regardless of farming system, environmentand fish health changes. It can be colonization during the larval fish rearing stage.Second, in the indoor farming system, the microecology niche of these bacteriachanged in the fish body, which may be the direct cause of disease occurrence.
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