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瘦素预处理对2型糖尿病大鼠心肌缺血再灌注损伤的保护作用

余 帆1，徐彤彤1，吕祥威2，佐 妍1，李 静1   

  1. 1.桂林医学院附属医院特需病区，广西 桂林 541001; 2.桂林医学院附属医院急诊科，广西 桂林 541001
  • 收稿日期:2013-05-02 发布日期:2013-12-12
  • 通讯作者: 徐彤彤 (Tel：0773-2807731，E-mail:xutongtongguilin@163.com) E-mail:xutongtongguilin@163.com
  • 作者简介:余 帆 (1988-)，女，湖南省岳阳市人，医师，医学硕士，主要从事心肌 缺血再灌注损伤的研究。 
  • 基金资助:

    广西壮族自治区科技厅自然科学基金资助课题（2012GXNSFAA502001）；
              广西科学研究与技术开发计划项目资助课题（桂科攻1140003B-76）；
              桂林市科学研究与技术开发计划项目资助课题（20130120-1）

Protective effect of leptin pretreatment on myocardial ischemic
 reperfusion injury in type 2 diabetic rats

YU Fan,XU Tong-tong,LU Xiang-wei,ZUO Yan,LI Jing   

  1. YU Fan1,XU Tong-tong1,LU Xiang-wei2,ZUO Yan1,LI Jing1
  • Received:2013-05-02 Published:2013-12-12

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摘要：

目的：探讨瘦素预处理对2型糖尿病（T2DM）大鼠心肌缺血再灌注损伤（MIRI）的
影响，阐明瘦素对T2DM大鼠MIRI的保护作用机制。方法：60只健康SD大鼠随机分为正常对照
组（n=10）与糖尿病组（DM，n=50），分别用以普通饲料和高糖高脂饲料喂养4周，糖尿病组大鼠在4周末腹腔注射链脲佐菌素复制DM模型，取造模成功的40只大鼠再随机分为假手术组（DM sham operation）、心肌梗死模型组（DM-MIRI）和心肌梗死瘦素预处理组（DM-leptin+MIRI）、心肌梗死术后瘦素处理组（D
M-MIRI+leptin），每组各10只。正常对照组大鼠空腹取血清和心脏组织标本，而在心肌梗死手术后3 h取DM组大鼠血清和心脏组织标本，测定各组大鼠血清肿瘤坏死因子α（TNF-α）、脂质过氧化产物丙二醛（MDA）、超氧化物歧化酶（SOD）、空腹血糖（FBG）、瘦素水平和胰岛素抵抗指数（HOMA-IR）。结果：与正常对照组比较，DM组大鼠的FBG、FINS、TNF-α、MDA、瘦素水平与HOMA-IR均升高，SOD活性降低（P<0.01）；与假手术组比较，DM-MIRI组、DM-leptin+MIRI组和DM-MIRI+leptin组大鼠FBG、FINS、TNF-α、MDA、瘦素水平与HOMA-IR明显升高，SOD活性降低（P<0.01）；与DM-MIRI组比较， DM-leptin+MIRI组大鼠FBG、FINS、TNF-α、MDA、瘦素水平与HOMA-IR明显降低，SOD活性升高（P<0.01）。DM-MIRI组大鼠心肌组织损伤最为严重，心肌细胞肥大、变形，心肌纤维排列紊乱，呈不规
则分布，细胞结构依稀可见，心肌呈片状局灶性坏死有出血，并有大量炎症中性粒细胞聚集；DM-leptin+MIRI
组大鼠虽仍有心肌细胞肥大、心肌组织结构紊乱，但出血坏死灶与中性粒细胞聚集明显减少，
病变明显改善；而DM-MIRI+leptin组大鼠心肌细胞病变亦有相同改善，但程度不及DM-Leptin+MIRI组。结论：瘦素预处理可减少DM大鼠的MIRI，
发挥心肌保护作用，其作用可能与胰岛素抵抗(IR)状态的改善有关联。

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

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