褪黑激素通过TGF-β1/Smads信号通路对LPS诱导新生大鼠脑炎的影响  

Effects of melatonin on LPS-induced encephalitis in neonatal rats via TGF-β1/Smads signaling pathway

作　　者：吴丹 徐博文 曲海新[1] 袁二伟[1] WU Dan;XU Bowen;QU Haixin;YUAN Erwei(Neonatology of the First Affiliated Hospital of Hebei North University,Hebei,Zhangjiakou 075000,China;Intensive Care Unit of the First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei 075000,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重症科,河北张家口075000

出　　处：《中国优生与遗传杂志》2022年第4期564-569,共6页Chinese Journal of Birth Health & Heredity

基　　金：河北省卫计委科研课题(20180852)。

摘　　要：目的 探究褪黑激素治疗脂多糖(LPS)诱导新生大鼠脑炎的效果,及其对于转化生长因子β1(TGF-β1)/Smads信号通路的影响。方法 通过产前对孕鼠腹膜内注射LPS制备新生大鼠脑炎模型;注射Ibotenate诱导幼鼠(产后第4天)发生兴奋毒性病变。免疫荧光染色法观察褪黑激素对幼鼠小胶质细胞活化及凋亡的影响;Western blot检测内质网应激和自噬相关蛋白、TGF-β1、Smads蛋白表达;qRT-PCR检测相关mRNA的表达。结果 褪黑激素可以减轻新生脑炎大鼠的兴奋性毒性损伤;免疫荧光染色结果显示,褪黑激素可以降低新生脑炎大鼠小胶质细胞的活化和凋亡的表达。褪黑激素干预并不能逆转新生大鼠脑炎内质网应激及自噬相关蛋白的变化。LPS下调了Smads蛋白的表达,上调了TGF-β1 mRNA的表达,褪黑激素可以逆转这些变化。结论 褪黑激素可能通过TGF-β1/Smads信号通路治疗LPS诱导的新生大鼠脑炎。Objective To investigate the effect of melatonin on lipopolysaccharide(LPS)-induced encephalitis in neonatal rats and its effect on transforming growth factor-beta 1(TGF-β1)/Smads signaling pathway. Methods The neonatal rats encephalitis model was established by intraperitoneal injection of LPS into pregnant rats before delivery, and the excitotoxic lesions of young rats(4 d after delivery) were induced by intraperitoneal injection of Ibotenate. Immunofluorescence staining was used to observe the effect of melatonin on the activation and apoptosis of microglia in young mice. Western blot was used to detect the expression of endoplasmic reticulum stress and autophagy-related protein, TGF-β1 and Smads protein,and qRT-PCR was used to detect the expression of mRNA in related genes. Results Melatonin could alleviate the excitotoxicity injury in neonatal encephalitis rats. Immunofluorescence staining results showed that melatonin could reduce the activation and apoptosis of microglia in neonatal encephalitis rats. Melatonin intervention could not reverse the changes of endoplasmic reticulum stress and autophagy-related proteins in neonatal rats with encephalitis. LPS down-regulated the expression of Smads protein and up-regulated the expression of TGF-β1. Melatonin could reverse these changes. Conclusion Melatonin may treat LPS-induced encephalitis in neonatal rats through TGF-β1/Smads signaling pathway.

关 键 词：褪黑激素 内质网应激 自噬 新生儿 脑炎 

分 类 号：R722.1[医药卫生—儿科]