熊去氧胆酸对小鼠ACE2受体的影响及感染SARS-CoV2-的效果

Effects of ursodeoxycholic acid on ACE2 receptor and infection with SARS-CoV-2 in mice

在新型冠状病毒(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)感染过程中,验证使用熊去氧胆酸(ursodeoxycholic acid,UDCA)在BALB/c小鼠体内是否具有降低血管紧张素转化酶2(angiotensin-converting enzyme 2,ACE2)受体的作用及降低感染风险。UDCA通过灌胃给药方式连续治疗BALB/c小鼠7 d,治疗过程中每天取小鼠鼻甲骨和肺脏,并通过ELISA检测小鼠鼻甲骨和肺脏中ACE2含量的变化;另外使用UDCA对BALB/c小鼠进行灌胃预防1、4、7 d后,分别滴鼻感染SARS-CoV-2 C57MA14鼠适应株和SARS-CoV-2 Omicron DY1.1,攻毒后3 d取小鼠鼻甲骨和肺脏检测病毒载量评价预防效果;此外使用UDCA对滴鼻感染SARS-CoV-2 C57MA14鼠适应株后的BALB/c小鼠进行灌胃治疗3 d,取小鼠鼻甲骨和肺脏检测病毒载量评价治疗效果。UDCA可以降低BALB/c小鼠鼻甲骨和肺脏中ACE2的含量;用UDCA灌胃1、4、7 d后的预防组和病毒对照组的BALB/c小鼠的鼻甲骨和肺脏中的病毒载量无统计学差异;UDCA治疗组与病毒对照组的鼻甲骨和肺脏的病毒载量之间无统计学差异。UDCA可以降低老龄BALB/c小鼠鼻甲骨和肺脏中ACE2的含量,但用UDCA治疗的每日剂量和持续时间对小鼠感染SARS-CoV-2 C57MA14鼠适应株和SARS-CoV-2 Omicron DY1.1无明显影响。

In the course of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,to verify whether ursodeoxycholic acid(UDCA)can reduce angiotensin-converting enzyme 2(ACE2)receptor in BALB/c mice and reduce the risk of infection.UDCA was administered by intragastric administration to BALB/c mice for 7 d.During the treatment,the turbinate bones and lungs of mice were taken every day,and the changes of ACE2 content in the turbinate bones and lungs of mice were detected by ELISA.In addition,after 1,4 and 7 d of intragastric prophylaxis,BALB/c mice were infected with SARS-CoV-2 C57MA14 mouse adapted strain and SARS-CoV-2 Omicron DY1.1,respectively,after nasal inoculation,and viral load was detected on the turnings and lungs of mice 3 d after challenge to evaluate the preventive effect.In addition,UDCA was used to treat BALB/c mice infected with SARS-CoV-2 C57MA14 mouse adapted strain after nasal drops by gavage for 3 d,and the viral load of the mouse turbinate and lung was detected to evaluate the therapeutic effect.UDCA can decrease ACE2 content in turbinate and lung of BALB/c mice.However,after 1,4 and 7 d of UDCA intragastric administration,there was no statistical difference in viral load in turbinate and lung of BALB/c mice between the prevention group and the virus control group.There was no significant difference in the viral load of the turbinate and lung between the UDCA treatment group and the viral control group.UDCA could reduce the ACE2 content in the turnings and lungs of aged BALB/c mice,but the daily dose and duration of UDCA treatment had no significant effect on the mice infected with SARS-CoV-2 C57MA14 mouse adapted strain and SARS-CoV-2 Omicron DY1.1.