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辅酶 Q10 可提高脓毒症大鼠的存活率、肠系膜灌注、器官和血管功能。

Coenzyme Q10 improves the survival, mesenteric perfusion, organs and vessel functions in septic rats.

机构信息

Department of Pharmacology, Faculty of Medicine, Selcuk University, Konya, Turkey.

Department of Pharmacology, Faculty of Medicine, Yildirim Beyazit University, Ankara, Turkey.

出版信息

Biomed Pharmacother. 2017 Jul;91:912-919. doi: 10.1016/j.biopha.2017.05.017. Epub 2017 May 11.

Abstract

BACKGROUND

Coenzyme Q10 (CoQ10) is a naturally occurring, lipid-soluble antioxidant and an essential electron carrier in the mitochondrial respiratory chain. In sepsis, CoQ10 deficiency induced by mitochondrial failure can lead to hypoxia, hypoperfusion, oxidative organ damage and finally death. We aimed to investigate the effects of CoQ10 on survival, mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries in cecal ligation and puncture (CLP)-induced sepsis.

METHODS

Wistar rats were divided into Sham, CLP, Sham+CoQ10, CLP+CoQ10 subgroups. CoQ10 (10mg/kg/day) or vehicle (olive oil; 1mL/kg/day) was intraperitoneally injected for 15days. At 16th day, Sham or CLP operation was performed. 20h after the operations, MABF and phenylephrine responses of isolated aortic rings were measured. Tissue samples were obtained for histopathological and biochemical evaluations. Furthermore, survival rates were monitored throughout 96h.

RESULTS

CoQ10 prevented mesenteric hypoperfusion and aortic dysfunction induced by CLP. Survival rate was %0 at 46th h in CLP group, but in CLP+CoQ10 group it was 37.5% at the end of 96h. CLP-induced elevations of serum AST, ALT, LDH, BUN, Cr and inflammatory cytokine (tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) levels were blocked by CoQ10. CoQ10 restored the increased liver, lung, spleen and kidney malondialdehyde levels and as well as reduced liver and spleen glutathione levels. The protective effects of CoQ10 on multiple organ damage were also observed histopathologically.

CONCLUSIONS

CoQ10 showed protective effects in sepsis due to its preservative effects on mesenteric perfusion, aortic function and also its anti-inflammatory and antioxidative effects.

摘要

背景

辅酶 Q10(CoQ10)是一种天然存在的脂溶性抗氧化剂,也是线粒体呼吸链中电子载体的必需物质。在败血症中,线粒体功能衰竭导致的 CoQ10 缺乏会导致缺氧、低灌注、氧化损伤器官,并最终导致死亡。我们旨在研究 CoQ10 对盲肠结扎和穿刺(CLP)诱导的败血症中的存活率、肠系膜动脉血流(MABF)、血管反应性、氧化和炎症损伤的影响。

方法

Wistar 大鼠分为假手术(Sham)、CLP、Sham+CoQ10、CLP+CoQ10 亚组。CoQ10(10mg/kg/天)或载体(橄榄油;1mL/kg/天)腹腔注射 15 天。第 16 天进行 Sham 或 CLP 手术。手术后 20 小时,测量离体主动脉环的 MABF 和苯肾上腺素反应。获取组织样本进行组织病理学和生化评估。此外,整个 96 小时监测存活率。

结果

CoQ10 可预防 CLP 引起的肠系膜低灌注和主动脉功能障碍。CLP 组 46 小时的存活率为 0%,但 CLP+CoQ10 组在 96 小时结束时为 37.5%。CoQ10 阻断了 CLP 引起的血清 AST、ALT、LDH、BUN、Cr 和炎症细胞因子(肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6)水平的升高。CoQ10 还恢复了肝、肺、脾和肾中增加的丙二醛水平,并恢复了肝和脾中的谷胱甘肽水平。CoQ10 对多器官损伤的保护作用也在组织病理学上得到了观察。

结论

由于 CoQ10 对肠系膜灌注、主动脉功能的保护作用以及抗炎和抗氧化作用,它在败血症中表现出保护作用。

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