TLR4/miR-223/NLRP3信号通路的表达与脑卒中后抑郁大鼠海马炎症反应的关系  

Relation of the expression of TLR4/miR-223/NLRP3 signal pathway with hippocampal inflammation of post-stroke depression rats

作　　者：张珂凡 常昕 肖智骏 席富强[1] ZHANG Kefan;CHANG Xin;XIAO Zhijun;XI Fuqiang(The First Affiliated Hospital of Baotou Medical College,Baotou 014010,China;Baotou Medical College,Baotou 014040,China)

机构地区：[1]包头医学院第一附属医院,内蒙古包头014010 [2]包头医学院,内蒙古包头014040

出　　处：《中国实用神经疾病杂志》2024年第2期133-138,共6页Chinese Journal of Practical Nervous Diseases

基　　金：内蒙古自治区高等学校科学研究项目(编号:NJZY22087)。

摘　　要：目的探究Toll样受体4(TLR4)/miR-223/核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)信号通路的表达与脑卒中后抑郁(PSD)大鼠海马炎症反应的关系。方法30只3月龄SPF级健康雄性Sprague-Dawley大鼠分为假手术组,PSD模型组和TLR4抑制剂组,各10只。PSD模型组和TLR4抑制剂组建立PSD模型,TLR4抑制剂组给予0.3 mg/kg的TAK-242溶液腹腔注射,其余各组均腹腔注射等体积的生理盐水溶液,5次/周,连续4周。评定各组大鼠的神经行为学,ELISA法检测血清白介素-1β(IL-1β)和IL-10的表达水平,RT-PCR测定海马组织中TLR4/miR-223/NLRP3信号通路相关基因的表达,Western blot测定TLR4/miR-223/NLRP3信号轴蛋白的相对表达。结果与假手术组相比,PSD模型组和TLR4抑制剂组大鼠Longa评分以及血清IL-1β和IL-10的表达升高,糖水偏嗜比(SP)、移动情况(LA)显著降低(P<0.05);与PSD模型组相比,TLR4抑制剂组大鼠Longa评分以及血清IL-1β和IL-10的表达表达下降、LA和SP升高(P<0.05)。与假手术组相比,PSD模型组大鼠海马组织中TLR4 mRNA、miR-223和NLRP3 mRNA以及TLR4、NLRP3、IL-1β和IL-10蛋白的相对表达均显著升高(P<0.05);与PSD模型组相比,TLR4抑制剂组的TLR4 mRNA和NLRP3 mRNA以及TLR4、NLRP3、IL-1β和IL-10蛋白的相对表达显著降低,miR-223的表达显著升高(P<0.05)。结论TLR4/miR-223/NLRP3信号转导通路与PSD海马炎症反应密切相关,通过调控TLR4/miR-223/NLRP3信号转导通路可能成为临床防治PSD的新靶位和新思路。Objective To investigate the relation of expression of Toll-like receptor 4(TLR4)/miR-223/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)signal pathway with hippocampal inflammation of post-stroke depression(PSD)rats.Methods Thirty 3-month-old SPF healthy male Sprague-Dawley rats were divided into sham group,PSD model group and TLR4 inhibitor group,10 mice each.The PSD model was established in the PSD model group and TLR4 inhibitor group,the TLR4 inhibitor group received 0.3 mg/kg of TAK-242 solution intraperitoneally,and the remaining groups were injected intraperitoneally with equal volume of saline solution,5 times/week for 4 weeks.The neurobehavior of rats was assessed,expression levels of serum interleukin-1β(IL-1β)and IL-10 were measured by ELISA,the expression of TLR4/miR-223/NLRP3 signaling genes in hippocampus by RT-PCR,and relative expression of TLR4/miR-223/NLRP3 signaling axis was determined by Western blot.Results In the PSD model group and TLR4 inhibitor group,serum IL-1βand SP and mobility(LA)(P<0.05),the Longa score,serum IL-1βand IL-10 expression and LA and SP in the TLR4 inhibitor group compared with the PSD model group(P<0.05).Relative expression of TLR4 mRNA,miR-223 and NLRP3 mRNA,and TLR4,NLRP3,IL-1βand IL-10 proteins were increased in the hippocampus of rats in the PSD model group(P<0.05).TLR4 mRNA and NLRP3 mRNA and TLR4,NLRP3,IL-1βand IL-10 and miR-223 compared with the PSD model group(P<0.05).Conclusion TLR4/miR-223/NLRP3 signal pathway is closely related with hippocampal inflammation of PSD,which could be potential new target and new thought for clinical prevention and treatment of PSD by regulation of TLR4/miR-223/NLRP3 signal pathway.

关 键 词：脑卒中后抑郁 炎症反应 海马 TLR4/miR-223/NLRP3信号通路 SPRAGUE-DAWLEY大鼠 

分 类 号：R-332[医药卫生]