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晚期糖基化终产物在2型糖尿病患者缺血性和扩张型心肌病发生发展中的作用

Advanced glycation end products in the development of ischemic and dilated cardiomyopathy in patients with diabetes mellitus type 2.

作者信息

Nozyński J, Zakliczyński M, Konecka-Mrówka D, Nikiel B, Mlynarczyk-Liszka J, Zembala-Nozyńska E, Lange D, Maruszewski M, Zembala M

机构信息

Department of Cardiac Surgery & Transplantation, Silesian Center for Heart Disease, Zabrze, Poland.

出版信息

Transplant Proc. 2009 Jan-Feb;41(1):99-104. doi: 10.1016/j.transproceed.2008.09.065.

DOI:10.1016/j.transproceed.2008.09.065
PMID:19249488
Abstract

INTRODUCTION

Hyperglycemia intensifies nonenzymatic glucose coupling to tissues, resulting in myocardial stiffness and formation of advanced glycation end products (AGE). The aim of this study was to assess seeking AGE in the myocardium from patients with type 2 diabetes (DM2) subjected to orthotopic heart transplantation (OHT), seeking to establish whether AGE play a role in the development of cardiomyopathies leading to OHT.

MATERIAL

The 2 studied groups consisted of 11 hearts explanted from patients with ischemic cardiomyopathy+DM2 (ICM+DM2, 55 +/- 6.5 years) and 8 from dilated cardiomyopathy+DM2 (DCM+DM2, 49.6 +/- 4.5 years). Comparative subgroups were composed of nondiabetic explanted hearts, 41 with ICM (52.8 +/- 5.8 years) and 41 with DCM (52.7 +/- 4.2 years). All patients were males.

METHODS

We examined immunohistochemical localization of AGE using a semiquantitative scale of reaction intensity in cardiomyocytes, fibroblasts, capillaries, arterioles, and arteries. Additionally, we calculated the scores for cardiocytes (AGE(Cardiocyte)) and all left ventricular components (AGE(LV)).

RESULTS

The cytoplasmic AGE deposits in cardiomyocytes were predominantly diffuse-granular in DM2 groups, whereas nondiabetic groups showed a lack of a reaction or a diffuse pattern. There were no differences in the reaction intensity between the 2 studied groups, or 2 comparative groups. All myocardial constituents showed higher AGE intensity in DM2 than nondiabetic groups. Only in the ICM+DM2 group did the DM2 duration correlate with AGE staining in selected myocardial layers and with AGE(Cardiocyte) and AGE(LV).

CONCLUSIONS

The presence of AGE in the hearts of patients requiring transplantation was related to the duration of DM2. The deposition of AGE in left ventricular myocardium was enhanced by DM2 particularly in patients with ICM.

摘要

引言

高血糖会加剧葡萄糖与组织的非酶偶联,导致心肌僵硬并形成晚期糖基化终产物(AGE)。本研究的目的是评估接受原位心脏移植(OHT)的2型糖尿病(DM2)患者心肌中AGE的情况,以确定AGE是否在导致OHT的心肌病发展中起作用。

材料

两个研究组分别由11例因缺血性心肌病合并DM2(ICM+DM2,55±6.5岁)患者的心脏和8例因扩张型心肌病合并DM2(DCM+DM2,49.6±4.5岁)患者的心脏组成。比较亚组由非糖尿病的心脏组成,41例ICM患者(52.8±5.8岁)和41例DCM患者(52.7±4.2岁)。所有患者均为男性。

方法

我们使用心肌细胞、成纤维细胞、毛细血管、小动脉和动脉中反应强度的半定量量表检查AGE的免疫组织化学定位。此外,我们计算了心肌细胞(AGE(心肌细胞))和所有左心室成分(AGE(左心室))的评分。

结果

DM2组心肌细胞中的细胞质AGE沉积物主要为弥漫颗粒状,而非糖尿病组则无反应或呈弥漫性模式。两个研究组或两个比较组之间的反应强度没有差异。所有心肌成分在DM2组中的AGE强度均高于非糖尿病组。仅在ICM+DM2组中,DM2病程与选定心肌层中的AGE染色以及AGE(心肌细胞)和AGE(左心室)相关。

结论

需要移植的患者心脏中AGE的存在与DM2病程有关。DM2会增强AGE在左心室心肌中的沉积,尤其是在ICM患者中。

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