研究报告
张玫,赵利芳,王影,苏瑞军,刘小娜,李卓玉,李瑞金.大气细颗粒物亚慢性染毒对大鼠肺内质网应激相关因子表达的影响[J].环境科学学报,2017,37(11):4444-4448
大气细颗粒物亚慢性染毒对大鼠肺内质网应激相关因子表达的影响
- Effects of subchronic exposure of ambient fine particulate matter on gene expressions of endoplasmic reticulum stress-related genes in lungs of rats
- 基金项目：国家自然科学基金（No.91543202）
- 作者
- 单位
- 张玫
- 山西大学环境科学研究所, 太原 030006
- 赵利芳
- 山西大学环境科学研究所, 太原 030006
- 王影
- 山西大学环境科学研究所, 太原 030006
- 苏瑞军
- 山西大学生物技术研究所, 太原 030006
- 刘小娜
- 山西大学生物技术研究所, 太原 030006
- 李卓玉
- 山西大学生物技术研究所, 太原 030006
- 李瑞金
- 山西大学环境科学研究所, 太原 030006
- 摘要：采集冬、夏季太原市大气细颗粒物（PM2.5），并制备PM2.5生理盐水混悬液.将35只雄性SD大鼠随机分为7组：对照组、3个不同剂量夏季PM2.5染毒组（0.2、0.6、1.5 mg·kg-1体重）及3个不同剂量冬季PM2.5染毒组（0.3、1.5、2.7 mg·kg-1体重），每组5只，气道滴注法染毒，每隔2 d染毒1次，共60 d.采用荧光实时定量PCR、Western blot、ELISA方法检测大鼠肺内质网应激指标——葡萄糖调节蛋白78（GRP78）、活化转录因子6（ATF6）、C/EBP同源蛋白（CHOP）、半胱氨酸天冬氨酸蛋白酶12（Caspase12）及血红素氧合酶-1（HO-1）的mRNA和蛋白表达变化.结果表明，与对照组相比，冬季中、高剂量PM2.5染毒组大鼠肺组织GRP78、ATF6、CHOP、Caspase12、HO-1 mRNA和蛋白表达显著增加，夏季高剂量PM2.5染毒组大鼠肺组织这5个基因mRNA和蛋白表达显著增加.冬季和夏季PM2.5组大鼠肺上述5个基因表达有剂量-效应关系.结果表明，太原市PM2.5亚慢性染毒可诱导大鼠肺内质网应激相关基因GRP78/ATF6/CHOP/HO-1表达，说明肺内质网应激反应加强；而CHOP和Caspase-12上调，提示与细胞凋亡关联的内质网相关性死亡途径被激活.冬季和夏季PM2.5引起内质网应激相关因子表达上调的效应没有显著差别.
- Abstract：Ambient fine particulate matter (PM2.5) was sampled from Taiyuan during winter and summer, and the PM2.5 physiological saline solutions were prepared. Thirty-five male SD rats were randomly divided into 7 groups: control group, three different doses of summertime PM2.5 groups (0.2, 0.6, 1.5 mg·kg-1 body weight) and three doses of wintertime PM2.5 groups (0.3, 1.5, 2.7 mg·kg-1 body weight) with five animals for each group. The rats were administered using PM2.5 solutions by intratracheal instillation respectively every three days for 60 days. And then the mRNA and protein expressions of the markers related to endoplasmic reticulum stress (ERS), including glucose-regulated protein 78 (GRP78), activated transcription factor 6 (ATF6), C/EBP homologous protein (CHOP), cysteine aspartic protease 12 (Caspase12) and heme oxygenase-1 (HO-1), were measured using real-time quantitative PCR, Western blot and ELISA in rat lungs after PM2.5 exposure. The results showed that the mRNA and protein expressions of GRP78, ATF6, CHOP, Caspase12, HO-1 in the lung tissues in medium-and high-dose PM2.5 groups in winter were significantly increased compared with the control group, while the expressions of the above 5 genes were significantly elevated in the high-dose PM2.5 group in summer compared to the control. There were dose-dependent effects of the expression increases of the above 5 genes in the winter or summer PM2.5 groups. These results suggest that the enhancement of ERS in the presence of PM2.5 from Taiyuan may be mediated by activating the ERS-related genes such as GRP78, ATF6, CHOP and HO-1, and that the up-regulation of CHOP and Caspase-12 might activate endoplasmic reticulum associated degradation pathway. In addition, no significant differences of mRNA and protein expressions of the ERS-related genes were observed in rat lungs between winter and summer PM2.5 groups.
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