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微小RNA146b对脓毒症小鼠炎症反应和脏器损伤的影响 被引量:10

Effects of MicroRNA-146b on Inflammatory Response and Organ Injury in Septic Mice
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摘要 目的观察微小RNA146b(miR-146b)对脓毒症小鼠炎症反应和脏器损伤的影响。方法选择健康雄性C57BL/6小鼠48只随机将其分为假伤组、脓毒症组、脓毒症miR-146b转染组及脓毒症对照转染组4组各12只,建立模型并给予相应处理。处理后24 h收集各组脏器组织标本及血清,检测比较各组心肌组织miR-146b水平,血清白细胞介素(IL)-1β、IL-6、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、肌酐(Cr)、尿素(BUN)水平,心肌组织中凋亡相关分子Cleaved-caspase 3、Bax蛋白水平,并观察比较各组肺脏及心脏病理组织形态。结果心肌组织miR-146b水平脓毒症组、脓毒症miR-146b转染组及脓毒症对照转染组均高于假伤组,脓毒症miR-146b转染组显著高于脓毒症组及脓毒症对照转染组;血清IL-1β、IL-6、ALT、AST、Cr、BUN水平及心肌组织中凋亡相关分子Cleaved-caspase 3、Bax蛋白水平脓毒症组、脓毒症miR-146b转染组、脓毒症对照转染组明显高于假伤组,脓毒症组、脓毒症对照转染组明显高于脓毒症miR-146b转染组,差异有统计学意义(P<0.05)。肺脏病理组织切片可见,与假伤组比较,脓毒症组肺泡结构破坏明显,炎性细胞浸润显著增加,假伤组肺泡无明显渗出,脓毒症组肺泡渗出显著;与脓毒症组比较,脓毒症miR-146b转染组肺泡结构改善,肺泡内渗出明显减少,炎性浸润减少。心肌病理组织切片可见,与假伤组比较,脓毒症组小鼠心肌结构紊乱,细胞肿胀,可见细胞核破碎;与脓毒症组比较,脓毒症miR-146b转染组心肌细胞排列较整齐,细胞无肿胀,未见明显碎裂细胞核。结论通过体内转染miR-146b可上调脓毒症小鼠脏器组织miR-146b水平,减少炎性因子产生,抑制炎症反应,减轻脏器损伤。 Objective To observe the protective effects of microRNA-146 b on inflammatory response and organ injury in septic mice model. Methods Forty-eight healthy male mice were divided into sham group,sepsis group,sepsis + miR-146 b group,and sepsis +sham-trans group according to the random number table,with 12 mice in each group. Cecal ligation and puncture( CLP) method was used to establish the septic model. After 24 hours,mice were sacrificed. Blood and organ tissues were harvested. The levels of miR-146 b,IL-1β,IL-6,ALT,AST,Cr,Bun,apoptosis-related cleaved-caspase3 and bax protein in myocardial tissues were measured. The pathological features of heart and lung were observed among different groups. Results The levels of miR-146 b in myocardium of the mice in sepsis group,sepsis + miR-146 b group and sepsis +sham-trans group were significantly higher than those in sham group. Specifically,the level of miR-146 b in myocardium of mice in sepsis + miR-146 b group was remarkably higher than that in sepsis group and sepsis +sham-trans group. The levels of IL-1β,IL-6,ALT,AST,Cr and Bun in serum and cleavedcaspase3 and bax protein in myocardium of mice were notably higher in sepsis group,sepsis + miR-146 b group and sepsis +sham-trans group than in sham group( P〈0. 05). Interestingly,the levels of these indicators were significantly higher in sepsis group and sepsis +sham-trans group than in sepsis + miR-146 b group( P〈0. 05). Histopathology of lung tissue sections showed that compared with the sham group,the alveolar structure of the sepsis group was significantly damaged,and inflammatory cell infiltration was significantly increased. By contrast,alveolar exudation was not significant in the sham group,but significant in the sepsis group. Compared with sepsis group,the alveolar structure of the sepsis miR-146 b transfection group was improved,the alveolar exudation was significantly reduced,and the inflammatory infiltration was reduced. Histopathology of myocardial tissue sections showed
作者 李林成 刘铭传 张家宁 曹梦远 朱朝娟 王倩梅 刘洋 鲍玫 李俊杰 LI Lin-cheng;LIU Ming-chuan;ZHANG Jia-ning;CAO Meng-yuan;ZHU Chao-juan;WANG Qian-mei;LIU Yang;BAO Mei;LI Jun-jie(a.Department of Emergency,b.Department of Burns and Cutaneous Surgery,Xijing Hospital,1.the Fourth Military Medical University,Xi'an 710032,China;the First Cadet Brigade,the Fourth Military Medical University,Xi'an710032,China;Department of Cardiothoracic Surgery,Bethune International Peace Hospital of PLA,Shijiazhuang 050082,China)
出处 《临床误诊误治》 2018年第5期102-108,共7页 Clinical Misdiagnosis & Mistherapy
基金 国家自然科学基金青年基金项目(81500492) 陕西省自然科学基础研究计划(2017JM8144)
关键词 脓毒症 小鼠 微小RNA146b 炎症反应 脏器损伤 Sepsis Mice MicroRNA-146b(miR-146b) Inflammatory reaction Organ injuries
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