Effect Of NOD2 On The Development Of Myocardial Hypertrophy Induced By Angiotensin ?

Objective This study was to investigate the effect of nucleotide-binding oligomerization domain 2(NOD2)on angiotensin II(AngII)-induced myocardial hypertrophy in mice.Methods Twenty-four male C57BL/6 mice,8 weeks old and weighing 24-26 g,were randomly divided into three groups: The normal control group(referred to as the control group),the angiotensin II + normal saline group(referred to as Ang II group),the angiotensin II + NOD2 protein inhibitor group(referred to as NOD2 inhibitor group),eight in each group.Each group of mice was subcutaneously implanted with miniature osmosis release pumps.AngII group and NOD2 inhibitor group were subcutaneously pumped into AngII at the rate of 1.3 mg/kg/day,At the same time,AngII group was intraperitoneally injected with normal saline 10ul/g every other day,and NOD2 inhibitor group was intraperitoneally injected with the 4mg/ml NOD2 inhibitor Pifithrin-u 10ul/g every other day.The control group was subcutaneously injected normal saline with an equal volume of AngII and intraperitoneally injected with normal saline 10ul/g every other day.After four weeks observation,the body weight was weighed,we opened the chest to remove the heart quickly,the whole heart mass was weighed and calculated the heart mass index [heart mass(mg)/ body weight(g),HMI].Divided the ventricle into equal three segments-the upper ventricle,the middle ventricle and the lower ventricle.The expression of ?-MHC mRNA in cardiomyocytes was detected by RT-qPCR in the upper ventricle;the middle ventricle was stained with Masson and Hematoxylin-Eosin(HE)respectively to detect the content of myocardial collagen fiber and the cross sectional area of cardiomyocytes;the protein expression level of NOD2 in cardiomyocytes was detected by Western Blot in the lower part of the ventricle.Results1 Changes of cardial hypertrophy and collagen fiber content in mice1.1 Changes in heart mass index(HMI)of mice in each group The HMI of AngII group was higher than that in the control group [(5.49±0.27)vs(4.05±0.11)mg/g,P<0.05];there was no significant difference in HMI between NOD2 inhibitor group and AngII group.[(5.48±0.25)vs(5.49±0.27)mg/g,P>0.05].1.2.Changes in cross-sectional area of cardiomyocytes of mice in each group The cross-sectional area of myocardial cells in AngII group was larger than that in control group [(414.28±89.17)vs(189.42±33.55)um2,P<0.05];there was no significant difference in the cross-sectional area of cardiomyocytes between the NOD2 inhibitor group and the AngII group [(427.14±75.90)vs(414.28±89.17)um2,P>0.05].1.3 Changes in myocardial collagen fiber volume fraction of mice in each group The volume fraction of myocardial collagen fibers in AngII group was higher than that in control group [(15.17±0.90)vs(2.21±0.30)%,P<0.05];there was no significant difference in the volume fraction of myocardial collagen fibers between the NOD2 inhibitor group and the AngII group [(15.15±0.86)vs(15.17±0.90)%,P>0.05].2 Changes of ?-MHC mRNA expression level in myocardial cells of mice The expression level of ?-MHC mRNA in AngII group was higher than that in control group[(1.73±0.19)vs 1,P<0.05];there was no significant difference in the expression level of ?-MHC mRNA between the NOD2 inhibitor group and the AngII group [(1.62±0.27)vs(1.73±0.19),P>0.05].3 Changes of NOD2 protein expression levels in myocardial cells of mice NOD2 protein expression level in AngII group was higher than that in control group[(1.45±0.12)vs(0.73±0.03),P<0.05];NOD2 protein expression level in NOD2 inhibitor group was lower than that of the AngII group [(1.06±0.07)vs(1.45±0.12),P<0.05].Conclusions1.AngII can induce myocardial hypertrophy in mice,and collagen fibers in myocardial hypertrophy increase.2.NOD2 was not associated with AngII-induced myocardial hypertrophy.