Comparison of two modeling methods In mice myocardial fibrosis model induced by micropump and subcutaneous injection of Ang Ⅱ
Objective:To compare the modelling methods of micropump implantation and subantaneous injection of Angiotensin Ⅱ(Ang Ⅱ),as well as the differences myocardial fibrosis induced by different doses in mice,and the optimal replication method of animal models was determined.Methods:Forty male C57BL/6 mice were randomly di-vided into blank control group,micropump group[micropump subcutaneous implantation of 1.5 mg/(kg·d)],sub-cutaneous group 1[subcutaneous injection of 1.5 mg/(kg·d)]and subcutaneous group 2[subcutaneous injection of 2.5 mg/(kg·d)],each group of 10,the blank group did not do any treatment,and the rest of the group was given Ang Ⅱfor 28 days,and the general state of the mice was observed.On the 28th day,electrocardiogram and echocardiography were performed to detect cardiac function,HE and Masson staining were used to observe the changes in cardiac theo-ry,serum BNP levels were detected by ELISA,and myocardial α-SM A,Collagen Ⅰ,and Collagen Ⅲ.protein expres-sions were detected by Western blot.Results:Compared with the blank control group,the general state and electrocar-diogram of mice in each administration group were the micropump group>the subcutaneous group>the subcutane-ous group 1.The left ventricular ejection fraction(EF)and left ventricular short-axis shortening rate(FS)decreased in the echocardiographic micropump group and subcutaneousgroup 2(all P<0.01),and the left ventricular end-dias-tolic internal diameter(LVIDd),left ventricular end-systolic diameter(LVIDs),left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),and left ventricular mass(LVd mass)increased(all P<0.05).In subcutaneous group 1,FS decreased(P<0.05),LVIDs and LVIDd increased(P<0.05),and EF was dif-ferent among groups(P<0.01).The serum natriuretic peptide(BNP)in the micropump group and subcutaneous group 2 was significantly increased(P<0.05),and there was no significant difference between the subcutaneous group 1 and the blank control group,and the difference between the administration groups was statistically significant(P<0.05).The inflammatory cell infiltration in the HE stained micropump group was significantly higher than that in the subcutaneous group,and the collagen fibre deposition stained by Masson staining was higher than that in the subcutaneous group 2(P<0.05),and there was no difference between the subcutaneous group 1 and the blank con-trol group(all P>0.05).The protein expressions of α-SMA,Collagen Ⅰ and Collagen Ⅲ were significantly increased in Western blot micropump group and subcutaneous group 2(P<0.05),while only α-SMA was increased in subcuta-neous group 1(P<0.05).Conclusion:Myocardial fibrosis models can be established by micropump at 1.5 mg/(kg·d)and subcutaneous injection at 2.5 mg/(kg·d)for 28 days,and the micropump group is significantly better than sub-cutaneous injection.Subcutaneous injection of 1.5 mg/(kg·d)induced myocardial fibrosis was not obvious.
Ang Ⅱmyocardial fibrosisModeling methodMicropump subcutaneous implantationSubcutane-ous injectionAnimal model