The Protective Effect Of Adiponectin On Adriamycin-induced Acute Cardiac Injury And The Relevant Mechanism

Objective:To investigate the anti-inflammatory action of adiponectin(APN)in adriamycin-induced acute cardiac injury and its relevant mechanism.Methods:1.Model construction Select 8-week-old male wild type C57 mice and pure APN knockout mice with similar body weight.Adriamycin in accumulation doses of 20mg·kg-1 was injected intraperitoneally to intervention groups.The control groups were given equal volume of saline once.During this period,all the mice were fed with sufficient regular chow.2.Animal grouping All the eligible mice were divided randomly into four groups: wild-type intervention group,wild-type control group,adiponectin intervention group,adiponectin control group.All the four groups were abbreviated as WT+ADM,WT+saline,KO+ADM,KO+saline,respectively.3.Experimental methods5 days after adriamycin administration,Serum and cardiac tissue samples were collected for the analysis of : serum level of biochemical index(by ELISA),the myocardial content of APPL1-AMPK?-PPAR?-OPN protein(by Western blotting),heart apical morphological changes(by HE staining)and location/distribution of inflammatory cells(by immunohistochemical assay).Statistical analysis was performed by using one way ANOVA and LSD-t test.Results:1.Compared with the WT+ADM group,the serum level of CK-MB and c Tn-I in APN-KO+ADM group were increased(CK-MK: 3.00±0.25 vs 3.35±0.47,P<0.05;c Tn-I: 77.66±64.30 vs 298.92±212.04,P<0.05).Compared with the APN-KO+saline group,their level in APN-KO+ADM group were increased(CK-MK: 2.95±0.15 vs3.35±0.47,P<0.05;c Tn-I: 54.46±24.58 vs 298.92±212.04,P<0.05).2.Compared with the WT+ADM group,the serum level of IL-6 and TNF-? in APN-KO+ADM group were increased(IL-6: 30.96±14.34 vs 71.71±51.51,P<0.05;TNF-?: 54.76±12.96 vs 100.01±19.57,P<0.05).Compared with the APN-KO+saline group,their level in APN-KO+ADM group were increased(IL-6: 35.15±25.17 vs71.71±51.51,P<0.05;TNF-?: 78.84±12.07 vs 100.01±19.57,P<0.05).There is no difference on serum level of TGF-? between all the four groups.3.The APPL1 cardiac content in APN-KO groups is significantly reduced compared to WT groups.AMPK? in APN-KO+ADM group is higher than APN-KO+saline group(1.20±0.28 vs 0.69±0.17,P<0.05).Compared with the WT+saline group,PPAR? in WT+ADM and APN-KO+saline is elevated(0.94±0.09 vs 1.69±0.24,P<0.05;0.94±0.09 vs 1.61±0.49,P<0.05).The difference of OPN between the four groups is significant(P<0.05).4.HE staining shows that besides two control groups,there is significant difference between the other groups(P<0.05).T cells and macrophages in the intervention groups are more,mainly distributed around vessels and scattered between cardiomyocytes.There is no difference between WT+ADM and WT+saline groups.All the other groups have significant difference(P<0.05).Conclusion:1.Results from this investigation suggest that adiponectin confers resistance to acute cardiac damage by suppressing cardiac inflammation.There is no difference in TGF-?,which may be the fibrosis activity is not obvious in the early stage of tissue damage,but systemic inflammation response dominates.2.Data presented here show that APPL1-AMPK?-PPAR?-OPN pathway participates in the early inflammation reaction of myocardial fibrosis change.APPL1 interacts directly with adiponectin receptors(Adipo R1 and Adipo R2).Adiponectin induces adenosine monophosphate–activated protein kinase(AMPK)activation by promoting APPL1-dependent LKB1 cytosolic translocation,then activated AMPK act on PPAR ?,lessen inflammation reaction and suppress inflammatory mediator release.PPAR ? regulate OPN transcription,and OPN work on macrophagocytes and myoblasts,which lead to advanced myocardial fibrosis.While macrophagocytes can produce OPN,form a vicious cycle.