Anti-infection effects of heparin on SARS-CoV-2 in a diabetic mouse model

作     者：Zhongyun Zhang 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 FGao Guang Ning Jiqiu Wang Yuhai Bi Zhongyun Zhang;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

作者机构：Department of Endocrinology and MetabolismShanghai Institute of Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai National Clinical Research Center for Metabolic DiseasesKey Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR ChinaShanghai National Center for Translational MedicineShanghai 200025China CAS Key Laboratory of Pathogen Microbiology and ImmunologyInstitute of MicrobiologyCenter for Influenza Research and Early-warning(CASCIRE)CAS-TWAS Center of Excellence for Emerging Infectious Diseases(CEEID)Chinese Academy of SciencesBeijing 100101China Laboratory Animal CenterChinese Center for Disease Control and Prevention(China CDC)Beijing 102206China Department of Respiratory and Critical Care MedicineInstitute of Respiratory DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Department of CardiologyInstitute of Cardiovascular DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China School of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhouZhejiang 325000China University of Chinese Academy of SciencesBeijing 100049China 

出 版 物：《Zoological Research》 (动物学研究（英文）)

年 卷 期：2023年第44卷第6期

页      面：1003-1014页

核心收录：

学科分类：1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 100401[医学-流行病与卫生统计学] 10[医学] 

基　　金：supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (CAS) (XDB29010102) National Natural Science Foundation of China (NSFC) (91957124,82161148010,32041010) Self-supporting Program of Guangzhou Laboratory (SRPG22-001) National Science and Technology Infrastructure of China (National Pathogen Resource Center-NPRC-32) Management Strategy of the Tertiary Prevention and Treatment of Diabetes Based on DIP system (supported by China Health Promotion Foundation) supported by the Youth Innovation Promotion Association of CAS (Y2021034) Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202208) 

主　　题：SARS-CoV-2 Diabetes Mouse model Heparin Antiviral therapy 

摘      要：Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and ***,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-Co V-2-infected diabetic patients remain *** investigate the disease pathogenesis,K18-h ACE2 transgenic(h ACE2^(Tg))mice with a leptin receptor deficiency(h ACE2-Lepr^(-/-))and high-fat diet(h ACE2-HFD)background were *** two mouse models were intranasally infected with a 5×10^(5) median tissue culture infectious dose(TCID_(50))of SARSCo V-2,with serum and lung tissue samples collected at 3days *** h ACE2-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 with1×10^(4) TCID_(50)of SARS-Co *** drug administration continued until the euthanasia of the *** of viral RNA loads,histopathological changes in lung tissue,and inflammation factors were *** demonstrated similar SARS-Co V-2 susceptibility in h ACE2^(Tg)mice under both lean(chow diet)and obese(HFD)***,compared to the h ACE2-Lepr^(+/+)mice,h ACE2-Lepr^(-/-)mice exhibited more severe lung injury,enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α(HIF-1α),and increased ***,combined LMWH and insulin treatment effectively reduced disease progression and severity,attenuated lung pathological changes,and mitigated inflammatory *** conclusion,preexisting diabetes can lead to more severe lung damage upon SARS-Co V-2 infection,and LMWH may be a valuable therapeutic approach for managing COVID-19patients with diabetes.