抑制miRNA-939表达减轻脓毒症大鼠肺肾损害的机制

IF 1.7 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Anwaier Apizi, Jian Li, Yan Li, Zhaoxia Yu, Ruifeng Chai
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引用次数: 0

摘要

败血症是一种由宿主反应失控引起的危及生命的疾病,可导致严重的器官功能障碍。MicroRNA 939 (miRNA-939)通过转录后调控NO/cGMP通路中关键酶的mRNA表达,在这一过程中发挥关键作用。这一途径在脓毒症难治性低血压和器官衰竭的发展中至关重要。本研究旨在探讨miRNA-939在盲肠结扎穿刺(CLP)大鼠肾肺脓毒症模型中的作用,以阐明其调节NO/cGMP通路的作用及其器官保护机制。材料与方法:为了探讨miRNA-939对脓毒症的影响,我们建立了三组大鼠:假手术组、脓毒症模型组和靶向miRNA-939的LNA- antimir治疗组,通过尾静脉注射给药(锁定核酸(LNA)组)。我们使用逆转录聚合酶链反应(RT-PCR)评估了血清、肾脏和肺部的miRNA-939水平。Western blotting检测诱导型一氧化氮合酶(iNOS)和可溶性鸟苷酸环化酶(sGC)蛋白水平。采用硝酸还原酶法测定血清一氧化氮(NO)水平。结果:与假手术组相比,脓毒症模型组大鼠血清miRNA-939水平明显升高,且在脓毒症诱导后12、24、36 h出现明显的峰值。同样,脓毒症组肾脏和肺部iNOS和sGC (sGCα1和sGCβ1亚基)蛋白水平明显升高。与假手术组相比,脓毒症组血清NO水平也显著升高。重要的是,在LNA组中抑制miRNA-939导致NO/cGMP通路中组织中iNOS、sGCα1、sGCβ1和血清NO水平的显著降低,同时减轻了肾脏和肺部的炎症损伤。结论:抑制miRNA-939可显著降低clp暴露大鼠NO/cGMP通路中iNOS、sGCα1、sGCβ1和NO的表达,从而减轻脓毒症中炎性器官的损害。这些发现突出了靶向miRNA-939在脓毒症诱导的器官功能障碍管理中的治疗潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mechanisms of alleviating sepsis-induced rat lung and kidney damage by inhibiting expression of miRNA-939.

Introduction: Sepsis, a life-threatening condition caused by a host response that goes out of control, leads to severe organ dysfunction. MicroRNA 939 (miRNA-939) plays a pivotal role in this process by post-transcriptionally regulating the mRNA expression of key enzymes in the NO/cGMP pathway. This pathway is crucial in the development of refractory hypotension and organ failure in sepsis. The aim of the study was to explore the effects of miRNA-939 on a caecum ligation puncture (CLP) rat model of sepsis in kidneys and lungs in order to elucidate its role in modulating the NO/cGMP pathway and related organ protection mechanisms.

Material and methods: To explore the effects of miRNA-939 on sepsis, we established three groups of rats: a sham surgery group, a sepsis model group, and an intervention group treated with LNA-antimiR targeting miRNA-939, which was administered via tail vein injection (the locked nucleic acid (LNA) group). We assessed miRNA-939 levels in serum, kidneys and lungs using a reverse transcription-polymerase chain reaction (RT-PCR). The protein levels of inducible nitric oxide synthase (iNOS) and soluble guanylate cyclase (sGC) were quantified using Western blotting. Serum nitric oxide (NO) levels were determined using the nitrate reductase method.

Results: Compared to the sham group, the rats in the sepsis model group exhibited significantly elevated levels of miRNA-939 in serum, with distinct peaks at 12, 24, and 36 h post-sepsis induction. Similarly, the protein levels of iNOS and sGC (sGCα1 and sGCβ1 subunits) in kidneys and lungs were markedly higher in the sepsis group. Serum NO levels were also significantly elevated in the sepsis group compared to the sham group. Importantly, inhibition of miRNA-939 in the LNA group led to a significant reduction in the tissue levels of iNOS, sGCα1, sGCβ1, and serum NO within the NO/cGMP pathway, alongside mitigating inflammatory damage to kidneys and lungs.

Conclusions: Inhibiting miRNA-939 significantly reduces the expression of iNOS, sGCα1, sGCβ1, and NO in the NO/cGMP pathway in CLP-exposed rats, thereby alleviating inflammatory organ damage in sepsis. These findings highlight the therapeutic potential of targeting miRNA-939 in the management of sepsis-induced organ dysfunction.

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来源期刊
Folia histochemica et cytobiologica
Folia histochemica et cytobiologica 生物-生化与分子生物学
CiteScore
2.80
自引率
6.70%
发文量
56
审稿时长
6-12 weeks
期刊介绍: "Folia Histochemica et Cytobiologica" is an international, English-language journal publishing articles in the areas of histochemistry, cytochemistry and cell & tissue biology. "Folia Histochemica et Cytobiologica" was established in 1963 under the title: ‘Folia Histochemica et Cytochemica’ by the Polish Histochemical and Cytochemical Society as a journal devoted to the rapidly developing fields of histochemistry and cytochemistry. In 1984, the profile of the journal was broadened to accommodate papers dealing with cell and tissue biology, and the title was accordingly changed to "Folia Histochemica et Cytobiologica". "Folia Histochemica et Cytobiologica" is published quarterly, one volume a year, by the Polish Histochemical and Cytochemical Society.
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