摘要
目的了解妊娠期、哺乳期及成年前持续氟铝联合染毒对子代大鼠骨组织内蛋白激酶R样内质网激酶(PERK)-酸化真核细胞起始因子2α(e IF2α)-激活转录因子4(ATF4)信号通路的影响。方法将36只健康成年清洁级SD孕鼠随机分为9组,分别为对照(自来水)组和氟化钠(60、240 mg/L)组、氯化铝(600、1 000 mg/L)单独染毒组及氟化钠+氯化铝联合染毒组,每组4只。采用自由饮水方式染毒,母鼠从妊娠第0天至子代大鼠出生第21天(postnatal day 21,PND21)染毒;每组随机选取8只子代大鼠继续以同组剂量染毒至PND90。染毒结束后,收集大鼠骨组织,以qRT-PCR法检测骨组织中ATF4和e IF2α的mRNA表达水平,ELISA测定骨组织中p-PERK、ATF4蛋白含量。结果与对照组比较,除低铝、高氟+低铝联合染毒组外,其余各染毒组子代大鼠骨组织中p-PERK蛋白含量明显升高(P<0.05);低氟组和低氟+高铝联合染毒组的ATF4蛋白含量高于对照组,差异有统计学意义(P<0.05)。氟铝联合染毒对p-PERK蛋白含量的影响表现为拮抗型交互作用(P<0.05);ATF4蛋白含量除高氟+低铝联合染毒组表现为协同型交互作用外,其他联合染毒组均表现为拮抗型交互作用(P<0.05)。除低氟组大鼠骨组织中e IF2αmRNA的表达明显升高外,其余染毒组明显降低(P<0.05)。除高氟+低铝联合染毒组大鼠骨组织中ATF4的mRNA表达明显升高外,其余各染毒组明显降低(P<0.05)。单独高氟或高铝染毒组比单独的低氟或低铝染毒组ATF4 mRNA表达量高,差异有统计学意义(P<0.05)。氟铝联合染毒对e IF2α及ATF4 mRNA表达水平的影响存在拮抗型交互作用(P<0.05)。结论氟铝联合可通过亲代胎盘屏障、乳汁及子代大鼠自身摄入等途径进入子代大鼠体内,诱发骨细胞内质网应激,PERK-e IF2α-ATF4信号通路参与了氟铝联合持续暴露的子代大鼠骨损伤机制。
Objective To know the effects of the continuous fluorine combined with aluminum exposure during gestation and lactation periods and before adulthood on the PERK-e IF2α-ATFF4 signal pathway in the offsprings＇ bone tissue. Methods Thirty-six pregnant SD rats were randomly divided into nine groups, four in each, control group（drinking tap water）, fluoride group（drinking the water containing sodium fluoride of 60 mg/L and 240 mg/L）, aluminum group（drinking the water containing aluminum chloride of 600 mg/L and 1 000 mg/L）, fluoride＋aluminum joint exposeur group. The pregnant rats were treated with fluoride or aluminum through drinking water from pregnant day 0 to postnatal day 21（PND21） of the offspring rats.Eight offspring rats were selected randomly in each group and were treated as above.The protein content of ATF4 and p-PERK were detected by ELISA; mRNA expression levels of ATF4 and e IF2α were measured with real time fluorescence quantitative polymerase chain reaction. Results In bone tissue of the offspring rats, compared with the control group,except the low aluminum group and the high fluoride combined with low aluminum group, p-PERK protein content markedly higher（P〈0.05）;There was increasing tendency of ATF4 protein content in every treated group, including significantly increases of ATF4 protein content in the low fluorine group and the low fluoride ＋high aluminum group（P〈0.05）. Combined effects of fluoride and aluminum on p-PERK protein content were antagonism interaction（P〈0.05）; Expect the synergism interaction of the combined effects of fluorine and aluminum on ATF4 protein content in the high fluoride＋low aluminum group, those in the other treated groups were antagonism interaction（P〈0.05）. The mRNA expression levels of e IF2α significantly increased in the low fluorine group, but markedly lowered in the other exposed groups（P〈0.05）. The mRNA expression levels of ATF4 significantly increased in the high fluoride ＋low aluminum group, where was markedly lowered in the other treated groups（P〈0.05）; The higher the single exposure dose of the fluorine or aluminum was, the higher the mRNA expression levels of ATF4 were, but it is on the contrary in the combined exposure groups（P〈0.05）. Combined effects of fluoride and aluminum on e IF2α and ATF4 expression level were antagonism interaction（P〈0.05）. Conclusion Fluoride combined with aluminum may go into the offspring rats through placental barrier and lactation and intake through the drinking water by the offspring rats themselves and induce endoplasmic reticulum stress in bone cells, PERK-e IF2α-ATF4 signal channel may be involved in the offspring rats bone cell damage caused by the continuous fluoride combined with aluminum exposure.
出处
《环境与健康杂志》
CAS
北大核心
2017年第4期301-304,共4页
Journal of Environment and Health
基金
国家自然科学基金(81560519)
关键词
氟
铝
蛋白激酶R样内质网激酶
酸化真核细胞起始因子2α
激活转录因子4
Fluorine
Aluminum
Protein kinase R-like ER kinase
Eukaryotic translation initiation factor 2α
Activating transcription factor-4
