河北医科大学学报 ›› 2024, Vol. 45 ›› Issue (11): 1301-1309.doi: 10.3969/j.issn.1007-3205.2024.11.011

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miR-96-5p通过调节JAK/STAT信号通路对2型糖尿病相关肺结核小鼠炎症反应的机制研究

  

  1. 黑龙江省传染病防治院结核内科三病区，黑龙江 哈尔滨 150500

  • 出版日期:2024-11-25 发布日期:2024-11-26
  • 作者简介:于文昭（1987-），女，回族，黑龙江哈尔滨人，黑龙江省传染病防治院主治医师，医学学士，从事结核内科疾病诊治研究。
  • 基金资助:
    黑龙江省教育厅科学技术研究项目（14251743）

The mechanism of miR-96-5p regulating inflammatory response of mice with type 2 diabetes mellitus-associated pulmonary tuberculosis via the JAK/STAT signaling pathway

  1. The Third Department of Tuberculosis, Infectious Disease Prevention and Control Hospital of Heilongjiang Province, Harbin 150500, China

  • Online:2024-11-25 Published:2024-11-26

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摘要： 目的 探讨miR-96-5p在2型糖尿病（type 2 diabetes mellitus，T2DM）相关肺结核（pulmonary tuberculosis，PTB）调节中的作用。
方法 构建T2DM相关PTB小鼠模型，实时定量反转录聚合酶链式反应分析miR-96-5p在T2DM相关PTB小鼠肺组织中的表达，Masson染色和HE染色分析肺纤维化和肺损伤情况；免疫组织化学和Western blot检测Janus激酶（Janus kinase，JAK）/信号传导及转录激活蛋白（signal transducer and activator of transcription，STAT）信号通路相关蛋白的表达；试剂盒分析血清中游离脂肪酸（free fatty acids,FFA）和三酰甘油水平。
结果 miR-96-5p在T2DM相关PTB小鼠肺组织中显著高表达，抑制miR-96-5p可以减轻肺组织的纤维化和肺损伤，降低T2DM相关PTB小鼠肺组织和血清中白细胞介素(interleukin, IL)-6、肿瘤坏死因子α（tumor necrosis factor-α，TNF-α）和IL-1β的水平，降低T2DM相关PTB小鼠肺组织中FFA和三酰甘油水平。p-JAK2和p-STAT3在T2DM相关PTB小鼠的肺组织中表达上调。JAK/STAT信号通路抑制剂（AZD1480）可以逆转miR-96-5p过表达对T2DM相关PTB小鼠模型中的肺纤维化和肺损伤的促进作用，可以减弱miR-96-5p过表达对T2DM相关PTB小鼠肺组织和血清中IL-6、TNF-α和IL-1β水平的促进作用，降低血清中FFA和三酰甘油水平。
结论 miR-96-5p通过调节JAK/STAT信号通路促进对T2DM相关PTB小鼠的炎症反应。


关键词: 糖尿病, 2型, 结核, 肺, 微RNAs

Abstract: Objective To investigate the role of miR-96-5p in the regulation of type 2 diabetes mellitus (T2DM)-associated pulmonary tuberculosis (PTB). 
Methods A T2DM-associated PTB mouse model was constructed. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze the expression of miR-96-5p in lung tissue of mice with T2DM-associated PTB. Masson staining and HE staining were used to analyze pulmonary fibrosis and lung injury. The expression of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway-related proteins was detected by immunohistochemistry and Western blot. The levels of free fatty acids (FFA) and triglyceride in serum were analyzed by kits. 
Results MiR-96-5p was highly expressed in the lung tissue of mice with T2DM-associated PTB. Inhibition of miR-96-5p could reduce fibrosis and lung injury in lung tissue, reduce the levels of interleukin (IL) -6, tumor necrosis factor-α (TNF-α) and IL-1β in lung tissue and serum of mice with T2DM-related PTB, and reduce the levels of FFA and triglyceride in lung tissue of mice with T2DM-related PTB. The expression of p-JAK2 and p-STAT3 was up-regulated in the lung tissue of mice with T2DM-related PTB. JAK/STAT signaling pathway inhibitor (AZD1480) could reverse the promoting effect of miR-96-5p overexpression on pulmonary fibrosis and lung injury in T2DM-related PTB mouse model, and could weaken the promoting effect of miR-96-5p overexpression on the levels of IL-6, TNF-α and IL-1β in lung tissue and serum of mice with T2DM-related PTB, and reduce the levels of FFA and triglyceride in serum. 
Conclusion miR-96-5p promotes inflammatory responses of mice with T2DM-associated PTB by regulating the JAK/STAT signaling pathway. 


Key words: diabetes mellitus, type 2, tuberculosis, pulmonary, microRNAs ,

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