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伊维菌素可降低小鼠实验模型中的体内冠状病毒感染。

Ivermectin reduces in vivo coronavirus infection in a mouse experimental model.

机构信息

Transgenic and Experimental Animal Unit, Institut Pasteur de Montevideo, Montevideo, Uruguay.

Cell Biology Unit, Institut Pasteur de Montevideo, Montevideo, Uruguay.

出版信息

Sci Rep. 2021 Mar 30;11(1):7132. doi: 10.1038/s41598-021-86679-0.

DOI:10.1038/s41598-021-86679-0
PMID:33785846
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8010049/
Abstract

The objective of this study was to test the effectiveness of ivermectin for the treatment of mouse hepatitis virus (MHV), a type 2 family RNA coronavirus similar to SARS-CoV-2. Female BALB/cJ mice were infected with 6,000 PFU of MHV-A59 (group infected, n = 20) or infected and then immediately treated with a single dose of 500 µg/kg ivermectin (group infected + IVM, n = 20) or were not infected and treated with PBS (control group, n = 16). Five days after infection/treatment, the mice were euthanized and the tissues were sampled to assess their general health status and infection levels. Overall, the results demonstrated that viral infection induced typical MHV-caused disease, with the livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while mice treated with ivermectin showed a better health status with a lower viral load (23,192 AU; p < 0.05), with only a few having histopathological liver damage (p < 0.05). No significant differences were found between the group infected + IVM and control group mice (P = NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in the treated mice than in the infected animals. In conclusion, ivermectin diminished the MHV viral load and disease in the mice, being a useful model for further understanding this therapy against coronavirus diseases.

摘要

本研究旨在测试伊维菌素治疗小鼠肝炎病毒 (MHV) 的效果,MHV 是一种类似于 SARS-CoV-2 的 2 型家族 RNA 冠状病毒。雌性 BALB/cJ 小鼠感染 6000 个感染性单位 (PFU) 的 MHV-A59(感染组,n=20)或感染后立即给予 500µg/kg 伊维菌素单剂量治疗(感染+IVM 组,n=20)或未感染并给予 PBS 治疗(对照组,n=16)。感染/治疗后 5 天,处死小鼠并取样评估其总体健康状况和感染水平。总的来说,结果表明病毒感染诱导了典型的 MHV 引起的疾病,肝脏出现严重的肝细胞坏死,周围伴有严重的淋巴浆细胞炎症浸润,与高肝病毒载量(52158AU)相关,而用伊维菌素治疗的小鼠表现出更好的健康状态,病毒载量较低(23192AU;p<0.05),只有少数小鼠有组织病理学肝损伤(p<0.05)。感染+IVM 组和对照组之间未发现显著差异(P=NS)。此外,治疗组小鼠血清转氨酶水平(天冬氨酸转氨酶和丙氨酸转氨酶)明显低于感染组。综上所述,伊维菌素降低了小鼠的 MHV 病毒载量和疾病程度,是进一步了解这种针对冠状病毒疾病的治疗方法的有用模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dad2/8010049/99e33600fd69/41598_2021_86679_Fig9_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dad2/8010049/d6e6534f294d/41598_2021_86679_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dad2/8010049/f03b705cedb1/41598_2021_86679_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dad2/8010049/99e33600fd69/41598_2021_86679_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dad2/8010049/1584b4adfa53/41598_2021_86679_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dad2/8010049/e38ce6b8144c/41598_2021_86679_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dad2/8010049/72bf6ddaf362/41598_2021_86679_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dad2/8010049/f49a026af11d/41598_2021_86679_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dad2/8010049/5e7eca240d36/41598_2021_86679_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dad2/8010049/633764af219d/41598_2021_86679_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dad2/8010049/d6e6534f294d/41598_2021_86679_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dad2/8010049/f03b705cedb1/41598_2021_86679_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dad2/8010049/99e33600fd69/41598_2021_86679_Fig9_HTML.jpg

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