本文選題：氟　切入點(diǎn)：鋁　出處：《環(huán)境與健康雜志》2017年04期 　論文類型：期刊論文

【摘要】：目的了解妊娠期、哺乳期及成年前持續(xù)氟鋁聯(lián)合染毒對(duì)子代大鼠骨組織內(nèi)蛋白激酶R樣內(nèi)質(zhì)網(wǎng)激酶(PERK)-酸化真核細(xì)胞起始因子2α(e IF2α)-激活轉(zhuǎn)錄因子4(ATF4)信號(hào)通路的影響。方法將36只健康成年清潔級(jí)SD孕鼠隨機(jī)分為9組,分別為對(duì)照(自來水)組和氟化鈉(60、240 mg/L)組、氯化鋁(600、1 000 mg/L)單獨(dú)染毒組及氟化鈉+氯化鋁聯(lián)合染毒組,每組4只。采用自由飲水方式染毒,母鼠從妊娠第0天至子代大鼠出生第21天(postnatal day 21,PND21)染毒;每組隨機(jī)選取8只子代大鼠繼續(xù)以同組劑量染毒至PND90。染毒結(jié)束后,收集大鼠骨組織,以qRT-PCR法檢測骨組織中ATF4和e IF2α的mRNA表達(dá)水平,ELISA測定骨組織中p-PERK、ATF4蛋白含量。結(jié)果與對(duì)照組比較,除低鋁、高氟+低鋁聯(lián)合染毒組外,其余各染毒組子代大鼠骨組織中p-PERK蛋白含量明顯升高(P0.05);低氟組和低氟+高鋁聯(lián)合染毒組的ATF4蛋白含量高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。氟鋁聯(lián)合染毒對(duì)p-PERK蛋白含量的影響表現(xiàn)為拮抗型交互作用(P0.05);ATF4蛋白含量除高氟+低鋁聯(lián)合染毒組表現(xiàn)為協(xié)同型交互作用外,其他聯(lián)合染毒組均表現(xiàn)為拮抗型交互作用(P0.05)。除低氟組大鼠骨組織中e IF2αmRNA的表達(dá)明顯升高外,其余染毒組明顯降低(P0.05)。除高氟+低鋁聯(lián)合染毒組大鼠骨組織中ATF4的mRNA表達(dá)明顯升高外,其余各染毒組明顯降低(P0.05)。單獨(dú)高氟或高鋁染毒組比單獨(dú)的低氟或低鋁染毒組ATF4 mRNA表達(dá)量高,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。氟鋁聯(lián)合染毒對(duì)e IF2α及ATF4 mRNA表達(dá)水平的影響存在拮抗型交互作用(P0.05)。結(jié)論氟鋁聯(lián)合可通過親代胎盤屏障、乳汁及子代大鼠自身攝入等途徑進(jìn)入子代大鼠體內(nèi),誘發(fā)骨細(xì)胞內(nèi)質(zhì)網(wǎng)應(yīng)激,PERK-e IF2α-ATF4信號(hào)通路參與了氟鋁聯(lián)合持續(xù)暴露的子代大鼠骨損傷機(jī)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 偽 IF2 偽 -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 偽 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 偽 mRNA in bone tissue of rats with low fluorine was significantly higher than that in low fluorine group, and the expression of e IF2 偽 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 偽 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 偽 -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.
【作者單位】： 貴州醫(yī)科大學(xué)公共衛(wèi)生學(xué)院環(huán)境衛(wèi)生學(xué)教研室;貴州醫(yī)科大學(xué)法醫(yī)病理學(xué)教研室;
【基金】：國家自然科學(xué)基金(81560519)
【分類號(hào)】：R114

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本文編號(hào)：1592982