基于mRNA测序筛选氟暴露大鼠主动脉组织PI3K/Akt/eNOS的基因表达差异  

Screening of mRNA expression differences of PI3K/Akt/eNOS in the aortic tissue of rats exposed to sodium fluoride based on mRNA sequencing

作　　者：孙洪娜 王腾 邹宁 王乔雨 高彦辉[1] 孙殿军 Sun Hongna;Wang Teng;Zou Ning;Wang Qiaoyu;Gao Yanhui;Sun Dianjun(Institute for Endemic Fluorosis Control,Center for Endemic Disease Control,Chinese Center for Disease Control and Prevention,Harbin Medical University,Harbin 150081,China;Central Laboratory,Center for Endemic Disease Control,Chinese Center for Disease Control and Prevention,Harbin Medical University,Harbin 150081,China;Center for Endemic Disease Control,Chinese Center for Disease Control and Prevention,Harbin Medical University,Harbin 150081,China)

机构地区：[1]哈尔滨医科大学中国疾病预防控制中心地方病控制中心地氟病防治研究所,150081 [2]哈尔滨医科大学中国疾病预防控制中心地方病控制中心中心实验室,150081 [3]哈尔滨医科大学中国疾病预防控制中心地方病控制中心,150081

出　　处：《中华地方病学杂志》2021年第12期953-956,共4页Chinese Journal of Endemiology

基　　金：国家自然科学基金(81673110)。

摘　　要：目的探索氟暴露对大鼠主动脉组织磷脂酰肌醇-3-激酶/蛋白激酶B/内皮型一氧化氮合酶(PI3K/Akt/eNOS)基因表达的影响, 为地方性氟中毒致心血管系统损伤的机制研究提供理论基础。方法将40只雄性Wistar大鼠按体质量(80 ~ 100 g)采用随机数字表法分成4组, 每组10只, 分别为对照组(饮用蒸馏水), 低、中、高剂量组[饮用含50、100、150 mg/L氟化钠(NaF)蒸馏水], 大鼠自由饮水摄食, 喂养90 d后处死, 取主动脉组织。对照组、高剂量组各取3份主动脉组织样本进行mRNA测序, 筛选差异基因, 并对差异基因进行GO功能富集分析和KEGG功能富集分析。同时, 采用实时荧光定量PCR检测各组大鼠主动脉组织PI3K、Akt、eNOS mRNA表达水平。结果高剂量组与对照组相比, 差异基因有756个, 其中上调基因有654个, 下调基因有102个。这些差异基因主要与肌肉收缩、肌肉调节、肌肉组织发育、横纹肌细胞发育、肌细胞分化、血液循环调节和横纹肌组织发育等生物过程相关, 主要富集于环磷酸鸟苷(cGMP-PKG)信号通路、松弛素信号通路、PI3K/Akt信号通路等。与对照组相比, 低、中、高剂量组大鼠主动脉组织PI3K、eNOS mRNA表达水平均较低(P均<0.05);低剂量组Akt mRNA表达水平较高(P<0.05)。结论氟暴露对大鼠主动脉组织的功能发挥和基因表达等生物过程具有一定的影响, PI3K/Akt/eNOS信号通路可能在氟致大鼠主动脉组织损伤过程中发挥重要作用。Objective To explore the effect of fluoride exposure on the gene expression of phosphatidylinositol-3-kinase/protein kinase B/endothelial nitric oxide synthase(PI3K/Akt/eNOS)in rat aortic tissue,and to provide a theoretical basis for studying the mechanism of cardiovascular injury caused by endemic fluorosis.Methods A total of 40 male Wistar rats were divided into 4 groups(10 rats in each group)via the random number table method according to body weight(80-100 g),namely control group(drinking distilled water),low-dose,medium-dose and high-dose groups[drinking distilled water containing 50,100 and 150 mg/L sodium fluoride(NaF),respectively].The rats were free to drink and eat.After feeding for 90 days,rats were sacrificed and the aortic tissue was taken.Three aortic tissue samples from the control group and the high-dose group were taken for mRNA sequencing,the differential genes were screened,and the differential genes were analyzed by GO function enrichment analysis and KEGG function enrichment analysis.At the same time,the mRNA expression levels of PI3K,Akt and eNOS in the aortic tissue of rats in each group were determined by real-time fluorescence quantitative PCR.Results Compared with control group,there were 756 differential genes in high-dose group,including 654 up-regulated genes and 102 down-regulated genes.These differential genes were mainly related to biological processes such as muscle contraction,muscle regulation,muscle tissue development,striated muscle cell development,muscle cell differentiation,blood circulation regulation and striated muscle tissue development.They were mainly enriched in cyclic guanosine phosphate(cGMP-PKG)signaling pathway,relaxin signaling pathway and PI3K/Akt signaling pathway,etc.Compared with control group,the mRNA expression levels of PI3K and eNOS in aortic tissue of rats in low-dose,medium-dose and high-dose groups were significantly reduced(P<0.05);the mRNA expression level of Akt in low-dose group was significantly increased(P<0.05).Conclusion Fluoride exposure has

关 键 词：氟 mRNA测序 主动脉 磷脂酰肌醇-3-激酶/蛋白激酶B/内皮型一氧化氮合酶信号通路 

分 类 号：R599.1[医药卫生—内科学]