摘要
目的观察γ-酮醛清道夫水杨胺(salicylamine,SAM)对尿毒症ApoE-/-小鼠动脉粥样硬化(atherosclerosis,AS)及其表型的影响。方法ApoE-/-小鼠通过5/6肾切除术建立尿毒症模型,对照组仅行假手术。实验动物分为对照组、尿毒症组及尿毒症SAM干预组,分别以SAM或安慰剂干预6周。干预结束后检测体质量、血压、血脂、肾功能、血清SAM浓度、主动脉AS斑块面积及斑块组分。结果与对照组相比,尿毒症组主动脉AS病变面积明显增大,AS斑块组分中坏死面积增大,巨噬细胞含量增多,胶原含量减少。SAM干预6周,尿毒症小鼠AS损伤面积、AS斑块中坏死面积及巨噬细胞含量减少,胶原含量增加,但不影响体质量、血压、血脂和肾功能,未发生药物蓄积和毒性作用。结论SAM能减轻尿毒症ApoE-/-小鼠加速发展的AS病变并使斑块的稳定性增加,这些作用不依赖于对血压、血脂或肾功能的影响,同时不引起药物蓄积及毒性作用。
Objective To observe the effect of aldehyde scavenger,salicylamine(SAM),on atherosclerosis(AS)and its phenotype in uremic apolipoprotein E knockout(ApoE-/-)mice.Methods Uremic ApoE-/-mice model was created by 5/6 nephrectomy;control ApoE-/-mice were sham-operated.Three subgroups of experimental mice were set up:uremia SAM intervention group,uremia group and control group,which were treated with SAM(1 g/L)or vehicle for 6 weeks,respectively.After the intervention was completed,we assessed the body weight,blood pressure,renal function,serum lipid profile,serum SAM concentration,extent and characteristic of aortic atherosclerotic lesion in each group of mice.Results Compared with control group:aortic AS lesion area,necrotic area and macrophage content in AS lesion increased but collagen content in AS lesion decreased in uremia group.SAM treatment for 6 weeks lessened the atherosclerotic lesion area,necrotic area and macrophage content of plaques,and meanwhile increased collagen content of plaques in uremic mice,not accompanied by changes in body weight,blood pressure,serum lipid profile or renal function.SAM did not accumulate or induce toxic effect on uremic ApoE-/-mice.Conclusion Aldehyde scavenger SAM ameliorates renal injury-induced acceleration of AS,alters atherosclerotic phenotype,and increases the stability of plaques.These benefits are independent of effects on blood pressure,lipid profile or renal function.SAM does not accumulate or induce toxic effect in uremic ApoE-/-mice.
作者
申燕
陈胜男
赵艳
VALENTINA Kon
SHEN Yan;CHEN Sheng-nan;ZHAO Yan;VALENTINA Kon(Department of Nephrology,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061;Department of Cardiovascular Medicine,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China;Department of Pediatric Nephrology and Hypertension,Vanderbilt University Medical Center,Nashville,TN 37232,USA)
出处
《西安交通大学学报（医学版）》
CAS
CSCD
北大核心
2020年第1期47-52,共6页
Journal of Xi’an Jiaotong University（Medical Sciences）
基金
国家自然科学基金资助项目(No.81200541)
陕西省卫生计生委计划资助项目(No.2016D064)
中央高校基本科研业务费专项资金资助项目(No.1191329725)
西安市科技计划资助项目(No.201805095YX3SF29)
国家留学基金资助项目(No.201506285033)~~
