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

Investigation of regulation and mechanism of miR-223 on autophagy of CD4+T lymphocytes in septic mice
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DOI:
10.14715/cmb/2020.66.7.32
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发表时间:
2020-01-01
影响因子:
1.6
通讯作者:
Ji, WenJie
Ji, WenJie
中科院分区:
生物学4区
文献类型:
--
作者:
Li, Qi;Xiang, Guoan;Ji, WenJie

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T淋巴细胞功能障碍是脓毒症免疫功能障碍的重要组成部分,其动态变化,尤其是CD 4 +T淋巴细胞的自噬与脓毒症的转归密切相关。本研究通过腹腔注射E. coli.120雄性C57 BL/6 J野生型。将20只雄性miR-223敲除(miR-223-/-)小鼠随机分为两组,分别腹腔注射生理盐水(NS)和E.大肠杆菌液组、生理盐水(WT NS)组、脓毒症(WT Sep)组、miR-223 -/- NS组和miR-223 -/- Sep组。采用流式细胞仪检测自噬相关蛋白的表达,观察CD 4 +T淋巴细胞自噬情况。流式细胞术显示WT Sep组小鼠外周血循环、肺泡和脾脏中的CD 4 + T淋巴细胞比例在术后逐渐下降,该细胞群中具有自噬活性的细胞比例明显高于WT NS组,并且miR-223 -/-小鼠中具有活跃自噬活性的CD 4 + T淋巴细胞的比例显著降低,但高于miR-223 -/- NS组,低于野生型小鼠CD 4 + T细胞自噬水平。因此,miR-223可上调脓毒症小鼠CD 4 + T淋巴细胞自噬水平,提示miR-223可能作为脓毒症防治的潜在靶点。
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.