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糖尿病大鼠心肌中 IPO 的消失与琥珀酸脱氢酶-黄素蛋白的增加有关。

The disappearance of IPO in myocardium of diabetes mellitus rats is associated with the increase of succinate dehydrogenase-flavin protein.

机构信息

Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003, Guizhou, People's Republic of China.

Anesthesia Laboratory, Affiliated Hospital of Zunyi Medical University, Zunyi, People's Republic of China.

出版信息

BMC Cardiovasc Disord. 2021 Mar 17;21(1):142. doi: 10.1186/s12872-021-01949-z.

DOI:10.1186/s12872-021-01949-z
PMID:33731005
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7968298/
Abstract

BACKGROUND

The aim of the present study was to investigate whether the disappearance of ischemic post-processing (IPO) in the myocardium of diabetes mellitus (DM) is associated with the increase of succinate dehydrogenase-flavin protein (SDHA).

METHODS

A total of 50 Sprague Dawley rats, weighing 300-400 g, were divided into 5 groups according to the random number table method, each with 10 rats. After DM rats were fed a high-fat and -sugar diet for 4 weeks, they were injected with Streptozotocin to establish the diabetic rat model. Normal rats were fed the same regular diet for the same number of weeks. Next, the above rats were taken to establish a cardiopulmonary bypass (CPB) model. Intraperitoneal glucose tolerance test (IPGTT) and oral glucose tolerance test (OGTT) were used to detect whether the DM rat model was established successfully. Taking blood from the femoral artery to collect the blood-gas analysis indicators, and judged whether the CPB model is established. After perfusion was performed according to the experimental strategy, the area of myocardial infarction (MI), and serum creatine kinase isoenzyme (CK-MB) and cardiac troponin (CTnI) levels were measured. Finally, the relative mRNA and protein expression of SDHA was detected.

RESULTS

The OGTT and IPGTT suggested that the DM rat model was successfully established. The arterial blood gas analysis indicated that the CPB model was successfully established. As compared with the N group, the heart function of the IR group was significantly reduced, the levels of myocardial enzyme markers, the area of MI, as well as the relative mRNA and protein expression of SDHA, were all increased. As compared with the IR group, the CK-MB and CTnI levels in the IPO group, the MI area, relative mRNA and protein expression of SDHA decreased. As compared with the IPO group, the myocardial enzyme content in the DM + IPO group, the MI area and the relative mRNA and protein expression of SDHA increased. As compared with the DM + IPO group, in the DM + IPO + dme group, the myocardial enzyme content, area of MI and relative mRNA and protein expression were all decreased.

CONCLUSION

IPO can inhibit the expression of SDHA, reduce MIRI and exert a cardioprotective effect in the normal rats. However, the protective effect of IPO disappears in the diabetic rats. The inhibitor dme combined with IPO can increase the expression of SDHA and restore the protective effect of IPO in DM myocardia.

摘要

背景

本研究旨在探讨糖尿病(DM)心肌中缺血后处理(IPO)的消失是否与琥珀酸脱氢酶黄素蛋白(SDHA)的增加有关。

方法

将 50 只 300-400g 的 Sprague Dawley 大鼠按随机数字表法分为 5 组,每组 10 只。DM 大鼠高脂高糖饮食喂养 4 周后,腹腔注射链脲佐菌素建立糖尿病大鼠模型。正常大鼠给予相同的常规饮食喂养相同的周数。然后,上述大鼠被用于建立心肺旁路(CPB)模型。采用腹腔葡萄糖耐量试验(IPGTT)和口服葡萄糖耐量试验(OGTT)检测 DM 大鼠模型是否建立成功。从股动脉取血收集血气分析指标,并判断 CPB 模型是否建立。按实验策略进行灌注后,测量心肌梗死(MI)面积及血清肌酸激酶同工酶(CK-MB)和心肌肌钙蛋白(CTnI)水平。最后,检测 SDHA 的相对 mRNA 和蛋白表达。

结果

OGTT 和 IPGTT 表明 DM 大鼠模型建立成功。动脉血气分析表明 CPB 模型建立成功。与 N 组相比,IR 组心功能明显降低,心肌酶标志物水平、MI 面积以及 SDHA 的相对 mRNA 和蛋白表达均升高。与 IR 组相比,IPO 组 CK-MB 和 CTnI 水平、MI 面积、SDHA 的相对 mRNA 和蛋白表达降低。与 IPO 组相比,DM+IPO 组心肌酶含量、MI 面积和 SDHA 的相对 mRNA 和蛋白表达增加。与 DM+IPO+DME 组相比,DM+IPO+DME 组心肌酶含量、MI 面积和 SDHA 的相对 mRNA 和蛋白表达均降低。

结论

IPO 可抑制 SDHA 表达,减少 MIRI,在正常大鼠中发挥心脏保护作用。然而,IPO 的保护作用在糖尿病大鼠中消失。抑制剂 DME 联合 IPO 可增加 SDHA 的表达,恢复 IPO 在 DM 心肌中的保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f723/7968298/d619f76dcbf0/12872_2021_1949_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f723/7968298/d619f76dcbf0/12872_2021_1949_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f723/7968298/02854d5f0af3/12872_2021_1949_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f723/7968298/1fa1e267b8a9/12872_2021_1949_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f723/7968298/fe1f56b7c71e/12872_2021_1949_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f723/7968298/a9cb3fa2d3c0/12872_2021_1949_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f723/7968298/f26a74767d72/12872_2021_1949_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f723/7968298/9968e7c17b62/12872_2021_1949_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f723/7968298/d619f76dcbf0/12872_2021_1949_Fig8_HTML.jpg

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