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持续氟铝联合暴露对子代大鼠骨组织蛋白激酶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信号通路的影响

发布时间:2018-03-10 10:40

  本文选题: 切入点: 出处:《环境与健康杂志》2017年04期  论文类型:期刊论文


【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(P0.05);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(P0.05)。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(P0.05);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(P0.05)。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(P0.05)。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(P0.05)。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(P0.05)。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(P0.05)。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。
[Abstract]:Objective to understand the gestation period, The effects of combined fluoride and aluminum administration during lactation and before adulthood on the signal pathway of protein kinase R-like endoplasmic reticulum kinases PERKM-acidified eukaryotic cell initiation factor 2 伪 IF2 伪 -activated transcription factor 4mATF4 in rat bone were studied. Methods 36 healthy rats were enrolled in this study. Adult SD rats of clean grade were randomly divided into 9 groups. They were the control (tap water) group, the sodium fluoride 60 ~ (60) mg / L group, the aluminum chloride 600 000 mg / L group alone and the sodium chloride and aluminum chloride combined group, 4 rats in each group. Rats were exposed to postnatal day 21 (PND21) from day 0 of pregnancy to day 21 of birth, and 8 offspring of each group were randomly selected to continue to be treated with the same dose to PND90.After the exposure, bone tissue was collected. The level of mRNA expression of ATF4 and e IF2 伪 in bone tissue was detected by qRT-PCR method and the content of p-PERKN ATF4 protein in bone tissue was determined by Elisa. The content of p-PERK protein in bone tissue of the other groups was significantly higher than that of the control group, while the content of p-PERK protein in the low fluorine group and the low fluoride and high aluminum group was higher than that in the control group. The difference was statistically significant (P 0.05). The effect of combined fluoride and aluminum exposure on the protein content of p-PERK showed that the protein content of P0.05AATF4 was a synergistic interaction except that of high fluoride and low aluminum exposure group. All the other combined groups showed antagonistic interaction (P0.05A). The expression of e IF2 伪 mRNA in bone tissue of rats with low fluorine was significantly higher than that in low fluorine group, and the expression of e IF2 伪 mRNA was significantly increased in low fluorine group. In the other groups, the expression of ATF4 mRNA was significantly increased in the bone tissue of rats exposed to high fluoride and low aluminum. The expression of ATF4 mRNA was higher in the high fluoride or high aluminum groups than in the low fluoride or low aluminum exposure groups, and the expression of ATF4 mRNA in the other groups was significantly lower than that in the low fluoride or low aluminum exposure groups. The difference was statistically significant (P 0.05). There was an antagonistic interaction between fluoride and aluminum on the expression of e IF2 伪 and ATF4 mRNA. Conclusion the combination of fluoride and aluminum can enter the offspring of rats through placenta barrier, milk and offspring. The PERK-e IF2 伪 -ATF4 signaling pathway induced by endoplasmic reticulum stress in osteocytes is involved in the mechanism of bone injury in the offspring of combined fluoride and aluminum exposure.
【作者单位】: 贵州医科大学公共卫生学院环境卫生学教研室;贵州医科大学法医病理学教研室;
【基金】:国家自然科学基金(81560519)
【分类号】:R114

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相关期刊论文 前9条

1 李晓东;王晓庆;姚晓;;内质网应激和JNK信号通路在骨关节炎中的相关作用[J];中国骨与关节杂志;2016年07期

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