Study On The Damage Of Captopril To The Heart And Lungs Of HACE2 Hypertensive Mice Infected With SARS-COV-2

Objective:At present,the new coronavirus disease pandemic is posing a threat to global public health.The infection of SARS-CoV-2 in hypertensive patients may lead to more severe features of the new coronary pneumonia disease and even aggravate the mortality rate.There is no report to clarify the relationship between hypertensive patients and the new coronary pneumonia disease,and there is no report on whether the continued use of captopril antihypertensive drugs will aggravate heart or lung damage.Therefore,this article has conducted a series of studies to clarify whether or not taking captopril antihypertensive drugs in patients with hypertension after being infected with SARS-CoV-2 will damage the heart and lung tissues,and provide a certain theoretical basis for the clinical medication of hypertensive patients infected with SARS-CoV-2.Methods:In this study,C57/B6 mice were first administered captopril,and qPCR was used to determine whether captopril would affect the expression of mACE2 in the heart and lungs.Next,establish a hACE2 hypertensive mouse model,use this model to infect SARS-CoV-2,and finally administer captopril to the infection model.QPCR was used to detect the viral load in the heart and lung tissues and feces of infected mice to indicate the infection status of the mice,and then qPCR,Masson staining,hematoxylin-eosin staining,Western blotting experiment,and ELISA experiment were used to detect the index of cardiac fibrosis,heart pneumonia,cardiac collagen volume,and cardiac hypertrophy after infection in mice to determine the damage or inflammation of the heart and lungs,and to explore whether the administration of captopril will damage the heart and lung tissues of mice.Results:(1)Captopril treatment can increase the mRNA expression of mACE2 in the heart and lung tissues of C57BL/6 mice.The expression level of mACE2 in the heart of C57BL/6 mice increased on the 5th and 7th day after the administration of captopril;the expression level of mACE2 in the lung tissue increased after the 5th day of administration.(2)Successfully established hACE2 hypertensive mouse model.On the 14th day after implantation of Ang Ⅱ in hACE2 mice,both systolic and diastolic blood pressure increased by 50-60mmHg,but there was no significant difference in heart rate changes(3)Successfully established a SARS-CoV-2 infection model in hACE2 hypertensive mice.At the beginning of the infection,higher viral loads were successfully detected in the feces of mice in the SARS-CoV-2 group,Ang Ⅱ+SARS-CoV-2 group,and Ang Ⅱ+SARS-CoV-2+Cap group.It is difficult to detect SARS-CoV-2 in the feces of mice in the SARS-CoV-2 group after the 6th day of infection,but on the 7th day of infection,the virus was still present in the feces of mice in the Ang Ⅱ+SARS-CoV-2 group and the Ang Ⅱ+SARS-CoV-2+Cap group.In the heart,on the 3rd day of infection,the viral load of the SARS-CoV-2 group and the Ang Ⅱ+SARS-CoV-2+Cap group was higher than that of the AngⅡ mouse group.But on the 7th day of infection,except for the SARS-CoV-2+Cap group mouse heart can detect the virus,the other two groups did not detect the virus in the heart.In the lung tissue,on the third day of infection,the viral load of the SARS-CoV-2 group and the Ang Ⅱ+SARS-CoV-2+Cap group was higher than that of the Ang Ⅱ mouse group.On the 7th day of infection,the viral load in the lung of the Ang Ⅱ mouse group was higher than that of the other two groups of mice,which was the opposite of the result on the 3rd day.(4)After hACE2 hypertensive mice were infected with SARS-CoV-2 and captopril treatment,the expression of cardiac fibrosis markers TGFβ1 and COL1al increased,and the volume of cardiac collagen increased.However,captopril treatment reduced the number of mice with hyalinosis,inclusion bodies,myocardial inflammation and necrosis of the heart artery wall,and the hs-Ctn-I protein content in the plasma was reduced.(5)After captopril treatment in hACE2 mice,the mRNA expression level of inflammatory factor IL-1β in the lung tissues decreased,and the expression of inflammatory factors IL-1β and TGFβ1 protein decreased.Conclusion:Captopril can increase the expression of MACE2 in mice.Captopril administration can reduce the expression of inflammatory factors in the lung tissue of hACE2 mice,and can alleviate the inflammatory response after SARS-CoV-2 infection in hypertensive mice.The administration of captopril increased the expression of cardiac fibrosis markers and increased the volume of cardiac collagen in mice,but reduced the number of mice with hyalinosis,inclusion bodies,myocardial inflammation and necrosis of the cardiac artery wall,and plasma The hs-Ctn-I in the drug is reduced,and the effect of captopril on the heart needs to be further explored.It is also necessary to correctly guide the therapeutic effect of antihypertensive drugs in patients infected with SARS-CoV-2.Captopril treatment can increase the mRNA expression of mACE2 in the heart and lungs of C57BL/6 mice.Captopril treatment can reduce the expression of inflammatory factors in the lung tissue of hACE2 mice,and can alleviate the inflammatory response in hypertensive mice after SARS-CoV-2 infection.Captopril treatment increased the expression of cardiac fibrosis markers and increased the volume of cardiac collagen,but reduced the number of mice with hyalinosis,inclusion bodies,myocardial inflammation,and necrosis of the cardiac artery wall,and at the same time,reduced the hs-cTn-I in plasma,and the effect of captopril on the heart needs to be further explored to correctly guide the therapeutic effect of antihypertensive drugs in patients infected with SARS-CoV-2.