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糖尿病对脓毒症大鼠模型中细胞因子及氧化性器官损伤的影响。

Effects of diabetes on cytokines and oxidative organ injury in a rat model of sepsis.

作者信息

Uyanik M H, Albayrak A, Odabasoglu F, Karakus E, Ozden K, Polat B, Yayla M, Karamese M, Albayrak A, Yazgi H

机构信息

Department of Microbiology and Clinical Microbiology, Ataturk University School of Medicine, Erzurum, Turkey.

出版信息

Cell Mol Biol (Noisy-le-grand). 2012 Feb 16;58 Suppl:OL1623-31.

Abstract

We aimed to investigate how Diabetes Mellitus (DM) affects myeloperoxidase activity, antioxidant status, and lipid peroxidation using biochemical approaches in heart, liver, and lung and serum cytokine analyses, such as interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in rat with sepsis induced by a cecal ligation and puncture-induced (CLP) sepsis. The rats were divided into four groups: control group, diabetic group, sepsis group, and diabetic+sepsis group. DM was induced in the male Wistar albino rats by administration of alloxan. Polymicrobial sepsis was induced by cecal ligation and two-hole puncture. After alloxan administration, all groups of rats were allowed to recover for 1 month. CLP model was applied after 1 month recovery to group 3 and 4. IL-6 and TNF-α, were measured. Effects of antioxidant defenses on the DM and/or sepsis process, the antioxidant levels superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) were evaluated in heart, lung and liver tissues. The oxidant levels, such as lipid peroxidation (LPO) and myeloperoxidase (MPO) levels were also evaluated in tissues. We demonstrated DM to augment the level of oxidant and proinflammatory cytokines in lung, liver, and heart and also to exacerbate oxidative injury as assessed by increased LPO and MPO, and decreased GSH and SOD levels in a sepsis model. DM increased levels of proinflammatory cytokines while DM also resulted in significantly increased levels of proinflammatory cytokines following CLP. DM-increased plasma proinflammatory cytokines levels correlated positively with tissue oxidant levels, such as MPO and LPO levels in a rat abdominal sepsis model, based on CLP, which resulted in the exacerbation of oxidative organs injury.

摘要

我们旨在通过生化方法研究糖尿病(DM)如何影响心脏、肝脏、肺组织中的髓过氧化物酶活性、抗氧化状态和脂质过氧化,并分析血清细胞因子,如白细胞介素-6(IL-6)和肿瘤坏死因子α(TNF-α),该研究对象为经盲肠结扎和穿刺诱导(CLP)脓毒症的大鼠。将大鼠分为四组:对照组、糖尿病组、脓毒症组和糖尿病+脓毒症组。通过给予四氧嘧啶诱导雄性Wistar白化大鼠患糖尿病。通过盲肠结扎和两孔穿刺诱导多微生物脓毒症。给予四氧嘧啶后,让所有大鼠组恢复1个月。在恢复1个月后,对第3组和第4组应用CLP模型。检测IL-6和TNF-α。评估抗氧化防御对DM和/或脓毒症过程的影响,测定心脏、肺和肝脏组织中的抗氧化水平,如超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽(GSH)。还评估组织中的氧化水平,如脂质过氧化(LPO)和髓过氧化物酶(MPO)水平。我们证明,在脓毒症模型中,DM会增加肺、肝脏和心脏中的氧化剂和促炎细胞因子水平,还会通过增加LPO和MPO以及降低GSH和SOD水平来加剧氧化损伤。DM会增加促炎细胞因子水平,而在CLP后,DM还会导致促炎细胞因子水平显著升高。在基于CLP的大鼠腹部脓毒症模型中,DM升高的血浆促炎细胞因子水平与组织氧化剂水平(如MPO和LPO水平)呈正相关,这导致氧化器官损伤加剧。

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