产前二手烟 (SHS) 暴露与高级糖化终产物受体 (RAGE)

K. Curtis, Kelsey M. Hirshi, K. Tsai, Evan T Clark, Brendan M Stapley, B. Bikman, P. Reynolds, J. Arroyo
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摘要

在胎儿发育过程中接触二手烟(SHS)会导致出生后的负面影响,包括器官发育改变、新陈代谢改变和呼吸系统疾病风险增加。此前,我们发现在接受过 SHS 治疗的小鼠中,宫内生长受限(IUGR)的诱导依赖于高级糖化终产物受体(RAGE)的表达。此外,产前接触 SHS 会增加胎儿肺中 RAGE 的表达。我们的目的是确定产前 SHS 处理对 4 周龄和 12 周龄后代的产后影响。妊娠动物通过纯鼻给药系统(Scireq Scientific,加拿大蒙特利尔)接受为期 4 天(胚胎 14.5 天至 18.5 天)的 SHS 处理,并在 4 周或 12 周大时对后代进行评估。测量动物和器官的重量,并对肺部进行组织学鉴定。测量血压和心率,并测定对照组和治疗组动物肺部的 RAGE 蛋白表达。我们观察到以下结果:(1) 动物、肝脏和心脏重量在 4 周龄时明显下降;(2) 4 周龄动物的血压升高;(3) 4 周龄动物肺部的 RAGE 表达增加。我们的研究结果表明,在出生后 12 周,这些指标都有所改善,因此无论暴露于 RA 还是 SHS,这些指标都没有差异。经SHS产前处理的4周龄小鼠肺中RAGE表达量的增加表明,这种由烟雾介导的重要受体可能会在IUGR妊娠后引发成年疾病。
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Antenatal Secondhand Smoke (SHS) Exposure and the Receptor for Advanced Glycation End-Products (RAGE)
Exposure to secondhand smoke (SHS) during fetal development results in negative postnatal effects, including altered organ development, changes in metabolism, and increased risk of respiratory illness. Previously, we found the induction of intrauterine growth restriction (IUGR) dependent on the expression of the receptor for advanced glycation end-products (RAGE) in mice treated with SHS. Furthermore, antenatal SHS exposure increases RAGE expression in the fetal lung. Our objective was to determine the postnatal effects of antenatal SHS treatment in 4- and 12-week-old offspring. Pregnant animals were treated with SHS via a nose-only delivery system (Scireq Scientific, Montreal, Canada) for 4 days (embryonic day 14.5 through 18.5), and offspring were evaluated at 4 or 12 weeks of age. Animal and organ weights were measured, and lungs were histologically characterized. Blood pressure and heart rates were obtained, and RAGE protein expression was determined in the lungs of control and treated animals. We observed the following: (1) significant decreases in animal, liver, and heart weights at 4 weeks of age; (2) increased blood pressure in 4-week-old animals; and (3) increased RAGE expression in the lungs of the 4-week-old animals. Our results suggest an improvement in these metrics by 12 weeks postnatally such that measures were not different regardless of RA or SHS exposure. Increased RAGE expression in lungs from 4-week-old mice antenatally treated with SHS suggests a possible role for this important smoke-mediated receptor in establishing adult disease following IUGR pregnancies.
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