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利用严重联合免疫缺陷鼠建立犬心丝虫微丝蚴血症新型啮齿动物模型。

Development of a novel rodent model for dog heartworm microfilaremia using the severe-combined immunodeficiency mouse.

机构信息

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido, 080-8555, Japan.

Yanbaru Animal Clinic, Nago, Okinawa, 905-0019, Japan.

出版信息

Sci Rep. 2024 Jun 14;14(1):13741. doi: 10.1038/s41598-024-63165-x.

Abstract

Dirofilaria immitis is a mosquito-borne parasitic nematode that causes fatal heartworm disease in canids. The microfilariae are essential for research, including drug screening and mosquito-parasite interactions. However, no reliable methods for maintaining microfilaria long-term are currently available. Therefore, we used severe combined immunodeficiency (SCID) mice to develop a reliable method for maintaining D. immitis microfilaria. SCID mice were injected intravenously with microfilariae isolated from a D. immitis-infected dog. Microfilariae were detected in blood collected from the tail vein 218 days post-inoculation (dpi) and via cardiac puncture 296 dpi. Microfilariae maintained in and extracted from SCID mice showed infectivity and matured into third-stage larvae (L3s) in the vector mosquito Aedes aegypti. L3s can develop into the fourth stage larvae in vitro. Microfilariae from SCID mice respond normally to ivermectin in vitro. The microfilariae in SCID mice displayed periodicity in the peripheral circulation. The SCID mouse model aided in the separation of microfilariae from cryopreserved specimens. The use of SCID mice enabled the isolation and sustained cultivation of microfilariae from clinical samples. These findings highlight the usefulness of the SCID mouse model for studying D. immitis microfilaremia in canine heartworm research.

摘要

犬恶丝虫是一种通过蚊子传播的寄生线虫,会导致犬致命的心丝虫病。微丝蚴对于研究,包括药物筛选和蚊子-寄生虫相互作用,是必不可少的。然而,目前尚无可靠的长期维持微丝蚴的方法。因此,我们使用严重联合免疫缺陷(SCID)小鼠来开发一种可靠的方法来维持犬恶丝虫的微丝蚴。SCID 小鼠通过静脉内注射从感染犬恶丝虫的狗中分离出的微丝蚴。在接种后 218 天通过尾静脉采血和 296 天通过心脏穿刺检测到血液中的微丝蚴。从 SCID 小鼠中维持和提取的微丝蚴在埃及伊蚊传播媒介中具有感染力,并成熟为第三期幼虫(L3)。L3 可以在体外发育为第四期幼虫。来自 SCID 小鼠的微丝蚴在体外对伊维菌素有正常反应。SCID 小鼠中的微丝蚴在外周循环中表现出周期性。SCID 小鼠模型有助于从冷冻保存标本中分离微丝蚴。SCID 小鼠的使用实现了从临床样本中分离和持续培养微丝蚴。这些发现强调了 SCID 小鼠模型在犬心丝虫研究中研究犬恶丝虫微丝蚴血症的有用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90f1/11178764/25e96814ce92/41598_2024_63165_Fig1_HTML.jpg

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