中国病理生理杂志2026,Vol.42Issue(5):936-945,10.DOI:10.3969/j.issn.1000-4718.2026.05.011
鸢尾素经AMPK/mTOR通路调控自噬缓解新生大鼠高胆红素血症
Irisin alleviates hyperbilirubinemia in neonatal rats by regulating au-tophagy via AMPK/mTOR signaling pathway
摘要
Abstract
AIM:To investigate the mechanism by which irisin ameliorates hyperbilirubinemia in neonatal SD rats via regulation of autophagy through the adenosine 5'-monophosphate-activated protein kinase/mammalian target of ra-pamycin(AMPK/mTOR)signaling pathway.METHODS:Seven-day-old SD rats were randomly divided into the control group,model group,irisin(80 µg/kg)group,irisin+Compound C(5 µL)group,and Compound C group according to the random number table method,with 15 rats in each group.Administration was performed on days 7 and 10 respective-ly,and the body weight of neonatal rats was recorded daily.On day 11,neurobehavioral tests,HE staining for pathologi-cal morphology of hippocampal tissue,transmission electron microscopy for autophagy detection,and Western blot for pro-tein expression levels of AMPK,p-AMPK,mTOR,p-mTOR,microtubule-associated protein 1 light chain 3(LC3)-II/I,sequestosome 1(P62),and autophagy-related protein 1(Beclin-1),immunofluorescence for the expression of p-AMPK,p-mTOR,and LC3,and RT-qPCR for the mRNA levels of LC3,P62,and Beclin-1 were conducted.RESULTS:Com-pared with the control group,rats in the model group showed a significant decrease in body weight(P<0.01),significant-ly prolonged latencies in the neurobehavioral tests(P<0.01),disordered arrangement of hippocampal neurons with aggra-vated injury,reduced numbers of autophagosomes,and mitochondrial vacuolization.Futhermore,the protein expression levels of p-AMPK,Beclin-1,and LC3-II/LC3-I,as well as the mRNA expression levels of some related genes,were signif-icantly downregulated,whereas the expression levels of p-mTOR and P62 were significantly upregulated(P<0.01).In contrast,compared with the model group,rats in the irisin group showed a significant increase in body weight(P<0.01)and significant improvement in neurobehavioral abnormalities(negative geotaxis test,P<0.05;righting reflex test,P<0.01),along with increased numbers of autophagosomes and alleviated mitochondrial damage.Meanwhile,the expression of autophagy-related and pathway-associated molecules was significantly improved,whereas the expression of p-mTOR and P62 was significantly downregulated(P<0.05).Compared with the irisin group,these improvements were significantly at-tenuated in the irisin+Compound C group(P<0.05).However,compared with the Compound C group,some indicators were still improved.Among them,the difference in body weight between the irisin+Compound C group and the model group was not statistically significant(P>0.05).CONCLUSION:I risin can exert a neuroprotective effect in neonatal rats with hyperbilirubinemia by regulating autophagy through the AMPK/mTOR signaling pathway.关键词
高胆红素血症/鸢尾素/自噬/AMPK/mTOR信号通路Key words
hyperbilirubinemia/irisin/autophagy/AMPK/mTOR signaling pathway分类
医药卫生引用本文复制引用
刘娟,王佳城,李鑫,杨新宇,韩文浩,牛浩淼,赵含莹,姜仪,庞伟..鸢尾素经AMPK/mTOR通路调控自噬缓解新生大鼠高胆红素血症[J].中国病理生理杂志,2026,42(5):936-945,10.基金项目
2022年度黑龙江省自然科学基金联合引导项目(No.LH2022H092) (No.LH2022H092)