关键词: 瘦素预处理, 糖尿病, 心肌缺血再灌注损伤

Abstract:

Objective To investigate the effect of leptin pretreatment on myocardial ischemic reperfusion injury(MIRI) in type 2 diabetic(T2DM) rats,and to ex
plain the mechanism of the protective effect.Methods Sixty healthy SD rats were randomly divided
 into normal control group (n=10) and diabetes mellitus group (DM,n=50),the rats were fed  with basic
 diet and high fat/high sucrose diet for 4 weeks，respectively.The rats in DM group were injected with strepto  zotocin intrapetioneally to

construct DM model.40 DM rats were randomly divided into DM sham operation group (n=10),and DM-MIRI group (n=10), DM-leptin+MIRI group
(n=10),and DM-MIRI+leptin group (n=10).The blood and heart samples were obtained from the rats  with
 empty stomach in normal control group and 3 h  after reperfusion in DM group.The levels of serum tumor necrosisfactor-alpha(TNF-α),

malondialdehyde(MDA),superoxide dismutase(SOD),fasting blood glucose(FBG),leptin, and homeostasis model assessment-IR (HOMA-IR) of the rats in various groups were detected.Results Compared with normal control group,the levels of FBG,FINS,TNF-α,MDA,
leptin,and HOMA-IR of the  rats in DM group were increased,and the activities of SOD were decreased(P<0.01).Compared
with DM sham operation group,the levels of FBG,FINS,TNF-α,MDA,leptin,and HOMA-IR of the rats in DM-MIRI,DM-leptin+MIRI and DM-MIRI+leptin group were significantly increased,and the activities of SOD were decreased (P<0.01).Compared with DM-MIRI group,the levels of FBG,FINS,TNF-α,MDA,leptin,and HOMA-IR of the rats in

DM-leptin+MIRI group  were significantly decreased,and the activities of SOD were increased (P<0.01).
The myocardium tissue of rats in DM-MIRI  group had serious injuries,and the  myocardial cells  were hypertrophy and deformation,and the myocardium tissue was partly necrosis and hemorrhage,and the myocardial fibers were derangement,and the myocardial cells  were visible and ar
ranged loosely and disorderly with infiltration of inflammatory cells of rats in mesenchyme;the myocardial cells of the rats in DM-leptin+MIRI group were still hypertrophy and deformation,and the myocardial structure was disorder,however the hemorrhage,necrosis,and neutrophils aggregation of myocardial tissue were significantly reduced,and the lesions improved significantly;while the pathological changes of myocardial cells of  the  rats in DM-MIRI+lept
in group were less than  DM-leptin+MIRI group.Conclusion Leptin pretreatment may protect the myocardium tissue and  alleviate the MIRI in DM rats,which may be
related to  the improvement of insulin resistance (IR).

Key words: leptin pretreatment, diabetes mellitus, myocardial ischemic reperfusion injury