调控miR-155对凝血功能障碍模型幼鼠的干预效果及作用机制研究  

Intervention Effect and Mechanism of Regulating MiR-155 on Young Rats with Dysfunction of Blood Coagulation

作　　者：张雅静[1] 袁二伟[1] 曲海新[1] 郭华贤[2] ZHANG Ya-Jing;YUAN Er-Wei;QU Hai-Xin;GUO Hua-Xian(Department of Neonatology,The First Affiliated Hospital of Hebei North University,Zhangjiakou 075000,Hebei Province,China;Department of Pediatrics,The First Affiliated Hospital of Hebei North University,Zhangjiakou 075000,Hebei Province,China)

机构地区：[1]河北北方学院附属第一医院新生儿科,河北张家口075000 [2]河北北方学院附属第一医院儿科,河北张家口075000

出　　处：《中国实验血液学杂志》2024年第3期852-856,共5页Journal of Experimental Hematology

基　　金：2017年度河北省卫生健康委科研基金项目青年科技课题(20170787)。

摘　　要：目的:研究调控miR-155对凝血功能障碍模型幼鼠的干预效果及作用机制。方法:选取健康、清洁级SD雄性幼鼠26只,建立凝血功能障碍模型,成功24只随机分为模型、上调miR-155和下调miR-155共3组,每组各8只。实时荧光定量聚合酶链式反应检测各组幼鼠miR-155表达,观察各组幼鼠凝血因子水平、凝血指标变化,HE染色观察肝脏病理组织,Western blot法检测HMGB1-RAGE/TLRs-NF-κB信号通路相关蛋白表达。结果:与模型组比,上调miR-155组HMGB1、RAGE、TLR2、TLR4、NF-κB均明显增高(均P<0.05),而下调miR-155组表达均明显降低(均P<0.05)。与模型组比,上调miR-155组凝血因子Ⅱ、Ⅶ、Ⅸ、Ⅹ表达均明显降低(均P<0.05),而下调miR-155组均表达升高(均P<0.05)。三组凝血因子Ⅺ表达差异比较无统计学意义(P>0.05)。与模型组比,上调miR-155组凝血酶原时间、活化部分凝血活酶水平较低,纤维蛋白原水平较高(均P<0.05),而下调miR-155组正好相反。结论:下调miR-155能有效改善凝血功能障碍幼鼠凝血因子水平及凝血指标,抑制炎症反应,其作用机制可能与HMGB1-RAGE/TLRs-NF-κB信号通路有关。Objective:To investigate the intervention effect and mechanism of regulating miR-155 on young rats with dysfunction of blood coagulation.Methods:Twenty-six healthy and clean SD male rats were selected to establish the coagulopathy models.Twenty-four rats successfully established models and were randomly divided into three groups:model group,up-regulated miR-155 group and down-regulated miR-155 group,with 8 rats in each group.The expression of miR-155 was detected by real-time fluorescence quantitative polymerase chain reaction.The changes of coagulation factors and coagulation indicators were observed.Liver pathological tissues were observed by HE staining.The expressions of HMGB1-RAGE/TLRs-NF-κB signaling pathway related proteins were detected by Western blot.Results:Compared with model group,the expressions of HMGB1,RAGE,TLR2,TLR4 and NF-κB were significantly increased in up-regulated miR-155 group(all P<0.05),while decreased in down-regulated miR-155 group(all P<0.05).Compared with model group,the expressions of coagulation factorⅡ,Ⅶ,Ⅸ,andⅩwere significantly decreased in up-regulated miR-155 group(all P<0.05),while increased in down-regulated miR-155 group(P<0.05).There was no significant difference in the expression of coagulation factorⅪamong the three groups(P>0.05).Compared with model group,the levels of prothrombin time(PT)and activated partial thromboplastin time(APTT)were lower and fibrinogen(FIB)was higher in up-regulated miR-155 group(all P<0.05),while in the down-regulated miR-155 group they were opposite.Conclusion:Down-regulation of miR-155 can effectively improve coagulation factors and coagulation indexes and inhibit inflammation in young rats with dysfunction of blood coagulopathy,and the mechanism may be related to HMGB1-RAGE/TLRs-NF-κB signaling pathway.

关 键 词：微小RNA-155 凝血功能障碍 小鼠 作用机制 HMGB1-RAGE/TLRs-NF-κB信号通路 

分 类 号：R554[医药卫生—血液循环系统疾病]