王锃,苏丽,陈瑞庆,蓝瑞隆,傅冷西.miR-223通过抑制NLRP3防护小鼠急性放射性肺损伤[J].中华放射医学与防护杂志,2019,39(3):166-171
miR-223通过抑制NLRP3防护小鼠急性放射性肺损伤
MiR-223 protects mice from acute radiation-induced lung injury by inhibiting NLRP3
投稿时间:2018-10-09  
DOI:10.3760/cma.j.issn.0254-5098.2019.03.002
中文关键词:  微小核糖核酸-223  放射性肺损伤  NLRP3
英文关键词:miR-223  Radiation-induced lung injury  NLRP3
基金项目:福建省自然科学基金项目(2016J05182)
作者单位E-mail
王锃 福建医科大学附属第一医院中心实验室 放射生物福建省高等学校重点实验室, 福州 350005  
苏丽 福建医科大学附属第一医院放疗科, 福州 350005  
陈瑞庆 福建医科大学附属第一医院中心实验室 放射生物福建省高等学校重点实验室, 福州 350005 crq209ted@163.com 
蓝瑞隆 福建医科大学附属第一医院中心实验室 放射生物福建省高等学校重点实验室, 福州 350005  
傅冷西 福建医科大学附属第一医院中心实验室 放射生物福建省高等学校重点实验室, 福州 350005  
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中文摘要:
      目的 研究miR-223通过抑制NLRP3对小鼠急性放射性肺损伤的防护。方法 将40只雌性C57BL/6 J小鼠,按随机数表法将小鼠分成4个组:健康对照组、单纯照射组、照射+miR-223组和照射+阴性对照(NC)组,每组10只。其中3个照射组给予15 Gy X射线全肺单次照射,照射+miR-223组和照射+NC组自照射前1 d开始至照射后14 d,隔天尾静脉注射10 nmol miR-223 agomir或agomir-NC。照射后第14 d取肺组织标本,HE染色观察病理变化,免疫组织化学法观察IL-1β和IL-18的定位和表达,实时荧光定量PCR检测miR-223和NLRP3的表达,Western blot检测NLRP3和Caspase-1的表达,ELISA检测肺组织中IL-1β和IL-18的表达。结果 辐射导致小鼠肺组织内miR-223表达下降和NLRP3的表达升高,给予miR-223 agomir可以抑制NLRP3的升高,同时减轻肺部炎症。实验结果显示,与单纯照射组相比,miR-223可以减轻小鼠肺组织的急性炎症反应。使得肺组织中IL-1β和IL-18表达下降(t=10.16、6.00,P<0.05)。肺组织NLRP3 mRNA表达下降(t=3.22,P<0.05)。Western blot结果显示,与单纯照射组相比,照射+miR-223组的NLRP3,Caspase-1蛋白表达下降(t=12.47、4.95,P<0.05)。Elisa结果也表明,在照射+miR-223组中炎症因子IL-1β和IL-18表达下降(t=8.22、8.47,P<0.05)。结论 miR-223通过抑制NLRP3的表达,抑制炎症因子IL-1β和IL-18的分泌,减轻炎症反应,对急性放射性肺损伤具有保护作用。
英文摘要:
      Objective To investigate the radioprotective function and its mechanism of miR-223 in acute radiation-induced lung injury in mice. Methods Forty female C57BL/6 J mice were randomly divided into healthy control group, irradiation group, irradiation plus miR-223 group and irradiation plus NC group. Radiation groups were exposed with a single dose of 15 Gy of 6 MV X-rays delivered by a linear accelerator. The mice in drug group were administered by tail vein injection with miR-223 agomir or agomir-NC every other day from 1 d before irradiation to 14 d after irradiation. The lung tissue samples of mice were taken at 14 d post-irradiation. The pathological changes were observed by HE staining. The localization and expressions of IL-1β and IL-18 were observed by immunohistochemistry (IHC). Real-time PCR was used to detect miR-223, but NLRP3 mRNA expression in lung tissue. Western blot was used to detect the protein expressions of NLRP3 and Caspase-1, and ELISA assay was used to detect the expressions of IL-1β and IL-18 in lung homogenate. Results Radiation decreased the expression of miR-223, but increased the expression of NLRP3 in lung tissue. Administration of miR-223 agomir inhibited the expression of NLRP3 and attenuated lung inflammation. HE and IHC staining showed that miR-223 reduced the acute inflammatory response and the expressions of IL-1β and IL-18 in lung tissue compared with irradiation group (t=10.16, 6.00, P<0.05). The expressions of NLRP3 and Caspase-1 protein in lung tissue of irradiated plus miR-223 group was lower than that in the irradiation alone group (t=12.47, 4.95, P<0.05). ELISA assay also showed a decrease of inflammatory factors IL-1β and IL-18 in lung tissue homogenate of the irradiation plus miR-223 group (t=8.22, 8.47, P<0.05). Conclusions MiR-223 effectively reduces the secretion of radiation-induced inflammatory factors IL-1β and IL-18 by inhibiting the expression of NLRP3 in lung tissue of mice, and thus has protective effect on radiation-induced lung injury.
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