茵陈素调控HIF-1α/BNIP3通路对高胆红素血症新生大鼠模型神经损伤的保护作用  

Protective effect of capillarin on nerve injury in neonatal hyperbilirubinemia rat model by regulating HIF-1α/BNIP3 pathway

作　　者：欧小琴 龚春竹 郑忠梅 秦彦 曹明慧 OU Xiaoqin;GONG Chunzhu;ZHENG Zhongmei;QIN Yan;CAO Minghui(Department of Emergency,Chengdu Women’s and Children’s Central Hospital,Women’s and Children’s Central Hospital Affiliated to Medical College of University of Electronic Science and Techology of China,Chengdu Sichuan 611731,China;Department of Endocrine,Chengdu Women’s and Children’s Central Hospital,Women’s and Children’s Central Hospital Affiliated to Medical College of University of Electronic Science and Techology of China,Chengdu Sichuan 611731,China)

机构地区：[1]电子科技大学医学院附属妇女儿童医院成都市妇女儿童中心医院急诊科,四川成都611731 [2]电子科技大学医学院附属妇女儿童医院成都市妇女儿童中心医院内分泌科,四川成都611731

出　　处：《中国妇幼健康研究》2022年第3期73-80,共8页Chinese Journal of Woman and Child Health Research

基　　金：四川省卫生健康委员会科研课题(NO.18PJ047)。

摘　　要：目的探讨茵陈素调控HIF-1α/BNIP3通路对高胆红素血症新生大鼠模型神经损伤的保护作用,以期探索新生儿高胆红素血症的治疗机制。方法通过腹腔注射胆红素建立高胆红素血症新生大鼠模型,随机分为模型组、茵陈素组、BAY87-2243[缺氧诱导因子-1α(HIF-1α)抑制剂]组、茵陈素+BAY87-2243组,每组12只,另取12只SD新生大鼠腹腔注射等量生理盐水,设为对照组。分组处理后,用横木行走测试检测大鼠运动协调及整合能力,检测大鼠小脑神经元凋亡情况、血清中枢神经特异性蛋白(S100β)及神经元特异性烯醇化酶(NSE)水平、小脑组织凋亡蛋白(caspase-3、Bax)及自噬蛋白(Beclin-1、LC3B)、HIF-1α/BCL2/腺病毒E1B相互作用蛋白3(BNIP3)通路蛋白(HIF-1α、BNIP3)的表达水平。结果各组大鼠小脑神经元凋亡率及caspase-3、Bax、Beclin-1、LC3B、HIF-1α及BNIP3蛋白表达水平差异均有统计学意义(F值分别为101.447、76.904、94.253、113.717、112.062、109.716、128.531,P<0.05)。两两比较显示,模型组大鼠小脑神经元凋亡率及caspase-3、Bax、Beclin-1、LC3B、HIF-1α、BNIP3蛋白表达水平均高于对照组;茵陈素组大鼠小脑神经元凋亡率及caspase-3、Bax蛋白表达水平均分别低于模型组、茵陈素+BAY87-2243组,Beclin-1、LC3B、HIF-1α、BNIP3蛋白表达水平分别高于模型组、茵陈素+BAY87-2243组;BAY87-2243组小脑神经元凋亡率及caspase-3、Bax蛋白表达水平均分别高于模型组、茵陈素+BAY87-2243组,大鼠Beclin-1、LC3B、HIF-1α、BNIP3蛋白表达水平均分别低于模型组、茵陈素+BAY87-2243组,上述差异均有统计学意义(P<0.05)。结论茵陈素可激活HIF-1α/BNIP3通路,促进自噬作用,抑制胆红素诱导的新生大鼠小脑神经元凋亡。Objective To investigate the protective effect of capillarin on nerve injury in neonatal hyperbilirubinemia rat model by regulating HIF-1α/BNIP3 pathway,and explore the therapeutic mechanism of neonatal hyperbilirubinemia.Methods Neonatal hyperbilirubinemia rat model was established by intraperitoneal injection of bilirubin,and the rats were randomly divided into model group,capillarin group,BAY87-2243(hypoxia inducible factor-1α(HIF-1α)inhibitor)group,and capillarin+BAY87-2243 group,with 12 rats in each group.Another 12 rats in the control group were intraperitoneally injected with the same amount of normal saline.After grouping,the ability of motor coordination and integration was tested by the beam walking test,the apoptosis of cerebellar neurons,the serum levels of central nerve specific protein(S100β)and neuron specific enolase(NSE),the expression levels of apoptosis related proteins(caspase-3,Bax),autophagy related proteins(Beclin-1,LC3B)and HIF-1α/Bcl2/Adenovirus E1B 19kDa protein-interacting 3(BNIP3)pathway related proteins(HIF-1α,BNIP3)were detected.Results There were statistically significant differences in the apoptosis rate of cerebellar neurons,and the expression levels of caspase-3,Bax,Beclin-1,LC3B,HIF-1α,BNIP3 proteins in each group(F values were 101.447,76.904,94.253,113.717,112.062,109.716 and 128.531,respectively,P<0.05).Pairwise comparison showed that the apoptosis rate of cerebellar neurons,and the protein expression levels of caspase-3,Bax,Beclin-1,LC3B,HIF-1αand BNIP3 in the model group were higher than those in the control group.The apoptosis rate and the protein expression levels of caspase-3 and Bax in the capillarin group were lower than those in the model group and the capillarin+BAY87-2243 group,respectively.Compared with those in the model group and capillarin+BAY87-2243 group,the expression levels of Beclin-1,LC3B,HIF-1α,BNIP3proteins were higher in the capillarin group.The apoptosis rate of cerebellar neurons and the expression levels of caspase-3 and Bax protein in the BA

关 键 词：茵陈素 新生儿 高胆红素血症 HIF-1α/BNIP3通路 神经损伤 

分 类 号：R722[医药卫生—儿科]