在老鼠模型和患有慢性脏疾病的儿童中,素失调和心肌功能障碍
Loretta Z Reyes1,2, Pamela D Winterberg1,2, Roshan Punnoose George1,2
1Division of Pediatric Nephrology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Nutrients
|July 11, 2023
概括
心血管疾病是慢性病 (CKD) 的主要风险之一. 在CKD中,氨酸代谢被破坏,导致小鼠和儿童的心脏功能障碍.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 心脏病学 心脏病学
- 生物化学 生物化学
背景情况:
- 心血管疾病 (CVD) 是慢性病 (CKD) 患者的主要死亡原因.
- 氨酸是氧化 (NO) 合成的关键前体,在维持内皮和心肌功能方面起着至关重要的作用,其产生受到功能的显著影响.
- 氨酸生物可用性的失调与CKD中观察到的内皮和心肌功能障碍的发展有关.
研究的目的:
- 在CKD小鼠模型和CKD儿童中,研究阿尔金因代谢,氧化合成和心肌功能障碍之间的关系.
- 评估阿基纳酶活性和不对称二甲基氨基氨酸 (ADMA) 对慢性病患者心血管健康的影响.
主要方法:
- 来自129X1/SvJ小鼠的血样本 (有或没有第5/6切除术诱导的CKD) 和儿童 (有或没有CKD) 分析了氨基酸,ADMA和酶活性.
- 心声图被用来评估小鼠的心肌功能,这些测量与血分析结果相关联.
- 给患有CKD和没有CKD的小鼠注射了一种非特异性氨酶抑制剂,以评估其治疗潜力.
主要成果:
- 血中氨酸和谷氨胺度与CKD中心肌功能障碍的各种测量结果显著相关.
- 与健康对照组相比,随着时间的推移,在患有CKD的小鼠和接受透析的儿童中,阿基纳酶活性显著升高.
- 在CKD小鼠中,在阿基因酶抑制后,心室应变改善,在患有CKD的儿童中,ADMA水平增加与相对壁厚度 (RWT) 增加相关.
结论:
- 氨酸失调,以改变氨酸酶活性和ADMA水平为特征,在临床前小鼠模型和人类儿科CKD患者中与心肌功能障碍密切相关.
- 向阿基纳酶活性可能是缓解CKD心血管并发症的潜在治疗策略.
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