Anti-infection effects of heparin on SARS-CoV-2 in a diabetic mouse model
作者：Zhongyun Zhang, 上海交通大学医学院附属瑞金医院内分泌代谢病科, 上海 200025, 中国, Ning Zhang, Xuancheng Lu, Min Zhou, Xiaoxiang Yan, Weiqiong Gu, Jingru Yang, Qin Zhang, Cheng Zhang, Yuhuan Gong, Mingjun Jia, Xiaoyu Zhang, Peng Ning, Mei Liu, Xiaoyan Li, Xiaomeng Shi, Wenjun Liu, George F. Gao, Guang Ning, Jiqiu Wang, Yuhai Bi, 上海市内分泌代谢病研究所, 国家代谢性疾病临床医学研究中心, 上海 200025, 中国, 中国科学院微生物研究所, 病原微生物与免疫学重点实验室 & 中国科学院流感研究与预警中心, 北京 100101, 中国, 中国疾病预防控制中心实验动物中心, 北京 102206, 中国, 上海交通大学医学院附属瑞金医院呼吸与危重症医学科, 上海 200025, 中国, 上海交通大学医学院附属瑞金医院心内科, 上海 200025, 中国, 温州医科大学检验学院(生命科学学院), 浙江 温州 325000, 中国, 中国科学院大学, 北京 100049, 中国 · 发表于：动物学研究 · 年份：2023 · DOI：10.24272/j.issn.2095-8137.2023.108 · 被引用次数：6 · 研究领域：COVID-19 Clinical Research Studies、SARS-CoV-2 and COVID-19 Research、Adipokines, Inflammation, and Metabolic Diseases
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity. However, the precise mechanisms responsible for the combined impact of coronavirus disease 2019 (COVID-19) and diabetes have not yet been elucidated, and effective treatment options for SARS-CoV-2-infected diabetic patients remain limited. To investigate the disease pathogenesis, K18-hACE2 transgenic (hACE2 Tg ) mice with a leptin receptor deficiency (hACE2-Lepr -/- ) and high-fat diet (hACE2-HFD) background were generated. The two mouse models were intranasally infected with a 5×10 5 median tissue culture infectious dose (TCID 50 ) of SARS-CoV-2, with serum and lung tissue samples collected at 3 days post-infection. The hACE2-Lepr -/- mice were then administered a combination of low-molecular-weight heparin (LMWH) (1 mg/kg or 5 mg/kg) and insulin via subcutaneous injection prior to intranasal infection with 1×10 4 TCID 50 of SARS-CoV-2. Daily drug administration continued until the euthanasia of the mice. Analyses of viral RNA loads, histopathological changes in lung tissue, and inflammation factors were conducted. Results demonstrated similar SARS-CoV-2 susceptibility in hACE2 Tg mice under both lean (chow diet) and obese (HFD) conditions. However, compared to the hACE2-Lepr +/+ mice, hACE2-Lepr -/- mice exhibited more severe lung injury, enhanced expression of inflammatory cytokines and hypoxia-inducibl...