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早期生活应激会导致成年雄性大鼠的肾功能障碍,但不会导致成年雌性大鼠的肾功能障碍。

Early life stress induces renal dysfunction in adult male rats but not female rats.

机构信息

Section of Experimental Medicine, Georgia Health Sciences Univ., Augusta, GA 30912, USA.

出版信息

Am J Physiol Regul Integr Comp Physiol. 2013 Jan 15;304(2):R121-9. doi: 10.1152/ajpregu.00364.2012. Epub 2012 Nov 21.

Abstract

Maternal separation (MatSep) is a model of behavioral stress during early life. We reported that MatSep exacerbates ANG II-induced hypertension in adult male rats. The aims of this study were to determine whether exposure to MatSep in female rats sensitizes blood pressure to ANG II infusion similar to male MatSep rats and to elucidate renal mechanisms involved in the response in MatSep rats. Wistar Kyoto (WKY) pups were exposed to MatSep 3 h/day from days 2 to 14, while control rats remained with their mothers. ANG II-induced mean arterial pressure (MAP; telemetry) was enhanced in female MatSep rats compared with control female rats but delayed compared with male MatSep rats. Creatinine clearance (Ccr) was reduced in male MatSep rats compared with control rats at baseline and after ANG II infusion. ANG II infusion significantly increased T cells in the renal cortex and greater histological damage in the interstitial arteries of male MatSep rats compared with control male rats. Plasma testosterone was greater and estradiol was lower in male MatSep rats compared with control rats with ANG II infusion. ANG II infusion failed to increase blood pressure in orchidectomized male MatSep and control rats. Female MatSep and control rats had similar Ccr, histological renal analysis, and sex hormones at baseline and after ANG II infusion. These data indicate that during ANG II-induced hypertension, MatSep sensitizes the renal phenotype in male but not female rats.

摘要

母体分离(MatSep)是一种早期生命行为应激模型。我们曾报道过,MatSep 会加剧成年雄性大鼠的血管紧张素 II(ANG II)诱导性高血压。本研究旨在确定是否暴露于 MatSep 会使雌性大鼠对 ANG II 输注产生类似雄性 MatSep 大鼠的血压敏感性,并阐明 MatSep 大鼠中涉及该反应的肾脏机制。Wistar Kyoto(WKY)幼鼠在第 2 至 14 天期间每天接受 3 小时的 MatSep 处理,而对照组幼鼠则与母亲在一起。与对照组雌性大鼠相比,雌性 MatSep 大鼠的 ANG II 诱导的平均动脉压(MAP;遥测)升高,但与雄性 MatSep 大鼠相比,这种升高是延迟的。与对照组大鼠相比,雄性 MatSep 大鼠在基线和 ANG II 输注后,肌酐清除率(Ccr)降低。与对照组雄性大鼠相比,雄性 MatSep 大鼠的肾皮质 T 细胞增加,间质动脉的组织学损伤更大。与接受 ANG II 输注的对照组大鼠相比,雄性 MatSep 大鼠的血浆睾酮增加,雌二醇降低。去势的雄性 MatSep 和对照组大鼠的 ANG II 输注均未能增加血压。与接受 ANG II 输注的对照组大鼠相比,雌性 MatSep 和对照组大鼠的 Ccr、肾脏组织学分析和性激素在基线和 ANG II 输注后均相似。这些数据表明,在 ANG II 诱导的高血压期间,MatSep 会使雄性而非雌性大鼠的肾脏表型变得敏感。

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