臭氧能减轻链脲佐菌素诱导的糖尿病大鼠模型的心肌缺血再灌注损伤

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2024-09-20 DOI:10.2147/dddt.s482309

Mehmet Burak Gülcan, Hüseyin Demirtaş, Abdullah Özer, Zeynep Yığman, Ali Dogan Dursun, Mustafa Arslan, Gürsel Levent Oktar

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引用次数: 0

摘要

研究目的本研究旨在证明臭氧对链脲佐菌素（STZ）诱导的糖尿病大鼠心肌缺血再灌注损伤（IRI）是否具有心脏保护作用：将 38 只雄性 Wistar Albino 大鼠分为以下五组：对照组（C 组，n=6）、糖尿病组（D 组，n=6）、糖尿病臭氧组（DO 组，n=6）、糖尿病缺血再灌注组（DIR 组，n=6）、糖尿病缺血再灌注臭氧组（DIRO 组，n=6）。六只大鼠在此期间死亡，两只因手术并发症死亡。心肌缺血再灌注模型是通过从第四肋间切口建立的。使用 8- 0 prolene 缝线结扎 LAD 30 分钟。再灌注前5分钟腹腔注射臭氧（1毫克/千克）。再灌注时间为120分钟。再灌注结束后，进行心肌组织病理学检查和血清生化分析：结果：DIR 组 TUNEL（+）心肌细胞/HPF 的百分比明显高于 C、D 和 DO 组。相反，DIRO 组的 TUNEL 阳性率明显低于 DIR 组。DIR 组和 DIRO 组的 IRI 评分明显高于 C、D 和 DO 组。相比之下，DIRO 组的 IRI 损伤评分明显低于 DIR 组。DIR 组的血清 MDA 水平明显高于 C、D 和 DO 组。同样，DIRO 组的 MDA 水平也明显高于 C 组和 D 组。DIR 组的 CAT 活性明显高于 C 组和 D 组。DIR 组的 SOD 活性明显高于 C 组和 DO 组：我们的研究表明，臭氧通过抗氧化作用对 STZ 诱导的糖尿病大鼠的心脏具有保护作用。关键词：糖尿病；臭氧；心肌；SOD；MDA；缺血再灌注

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Ozone Administration Reduces Myocardial Ischemia Reperfusion Injury in Streptozotocin Induced Diabetes Mellitus Rat Model

Objective: This study aimed to demonstrate whether ozone has cardioprotective effects on the myocardial ischemia-reperfusion injury (IRI) in rats with streptozotocin(STZ)-induced diabetes.
Methods: A total of 38 male Wistar Albino rats were divided into five groups as follows: control group (group C,n=6), diabetic group (group D,n=6), diabetic ozone group (group DO,n=6), diabetic-ischemia/reperfusion (group DIR,n=6), diabetic-ischemia/reperfusion-ozone (group DIRO,n=6). Six rats died during this period and two died because of surgical complications. A myocardial ischemia-reperfusion model was created using a thoracotomy incision from 4th intercostal space. The LAD was ligated using an 8– 0 prolene suture for 30min. Ozone was administered intraperitoneally(1mg/kg) 5min before reperfusion. The reperfusion time was 120 min. At the end of the reperfusion procedure, myocardial tissue histopathological examinations, and serum biochemical analyses were performed.
Results: The percentage of TUNEL(+) cardiomyocytes/HPF was significantly higher in the DIR group than in the C, D, and DO groups. Conversely, TUNEL positivity was significantly lower in the DIRO group than in the DIR group. The IRI score was significantly higher in the DIR and DIRO groups than that in the C, D, and DO groups. In contrast, the IRI damage score in the DIRO group was significantly lower than that in the DIR group. Serum MDA levels were significantly higher in the DIR group than in the C, D, and DO groups. Similarly, MDA levels were significantly higher in the DIRO group than in the C and D groups. CAT activity was significantly higher in the DIR group than in the C and D groups. SOD activity was significantly higher in the DIR group than in the C and DO groups.
Conclusion: Our study showed that ozone exerts cardioprotective effects in STZ-induced diabetic rats through its antioxidant role against oxidative stress. Both biochemical and histological analyses clearly revealed that ozone has beneficial effects against IRI in the diabetic rat myocardium.

Keywords: diabetes mellitus, ozone, myocard, SOD, MDA, ischemia-reperfusion

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.