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miR-223 调控脓毒症小鼠 CD4+T 淋巴细胞自噬的作用及机制研究。

Investigation of regulation and mechanism of miR-223 on autophagy of CD4 + T lymphocytes in septic mice.

出版信息

Cell Mol Biol (Noisy-le-grand). 2020 Oct 31;66(7):207-215.

Abstract

T-lymphocyte dysfunction is most important part of immune dysfunction in sepsis, where dynamic change, especially autophagy of CD4+T lymphocytes is found to be related to disease fate. Our study is to i nvestigate the changes of CD4 + T lymphocytes and their autophagy levels in septic miR-223 -/- mouse model injected intraperitoneally with E. coli.120 male C57BL/6J wild-type. Twenty male miR-223 knockout(miR-223-/-) mice were randomly divided into, according to intraperitoneal injection of normal saline (NS) and E. coli solution, normal saline (WT NS) group, sepsis (WT Sep) group, miR-223 -/- NS group and miR-223 -/- Sep group, respectively. The autophagy related protein was monitored with flow cytometry to observe the autophagy of CD4+T lymphocytes. Flow cytometry showed the proportion of CD4 + T lymphocytes in peripheral blood circulation, alveoli, and spleen of mice in the WT Sep group gradually decreased after surgery, the proportion of cells with autophagic activity in this population of cells was significantly higher than that in the WT NS group, and the proportion of CD4 + T lymphocytes with active autophagic activity in miR-223 -/- mice were significantly decreased, but higher than that in the miR-223 -/- NS group and lower than the level of autophagy in CD4 + T cells of wild-type mice. Thus, miR-223 can up-regulate the level of autophagy in CD4 + T lymphocytes of septic mice, suggesting that miR-223 may be used as a potential target for the prevention and treatment of sepsis.

摘要

T 淋巴细胞功能障碍是脓毒症免疫功能障碍的最重要部分,其中发现 CD4+T 淋巴细胞的动态变化,尤其是自噬与疾病转归有关。我们的研究旨在探讨腹腔注射大肠杆菌后脓毒症 miR-223-/-小鼠模型中 CD4+T 淋巴细胞及其自噬水平的变化。120 只雄性 C57BL/6J 野生型小鼠,20 只雄性 miR-223 敲除(miR-223-/-)小鼠,随机分为腹腔注射生理盐水(NS)和大肠杆菌溶液,生理盐水(WT NS)组、脓毒症(WT Sep)组、miR-223-/- NS 组和 miR-223-/- Sep 组,分别。通过流式细胞术监测自噬相关蛋白,观察 CD4+T 淋巴细胞的自噬情况。流式细胞术显示,WT Sep 组小鼠外周血循环、肺泡和脾脏中的 CD4+T 淋巴细胞比例在手术后逐渐下降,该细胞群体中具有自噬活性的细胞比例明显高于 WT NS 组,miR-223-/- 小鼠中具有活性自噬活性的 CD4+T 淋巴细胞比例明显降低,但高于 miR-223-/- NS 组,且低于野生型小鼠 CD4+T 细胞的自噬水平。因此,miR-223 可上调脓毒症小鼠 CD4+T 淋巴细胞的自噬水平,提示 miR-223 可能成为脓毒症防治的潜在靶点。

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