氨基酸保护肾小管细胞溶酶体功能的研究

Lysosomal Autophagia in Experimental Nonoliguric Acute Renal Failure and Protection by Amino Acids in Rats

目的 :研究肾小管细胞溶酶体损伤在顺铂所致实验性 ARF发病中的作用 ,探讨 8种 L-氨基酸合剂的肾功能保护作用及机理。方法 :雄性 Sprague- Dawley鼠静脉注射 2 ml氨基酸合剂或0 .9% Na Cl溶液后接受 10 mg/ kg顺铂 ,随后氨基酸或 Na Cl溶液以 2 ml/ h维持 3h,测定尿 NAG活性 ,尿钠、钾浓度 ,GFR及作形态学观察。结果 :顺铂注射后 30 min,尿 NAG活性增加 7.8倍 ,尿钠、钾浓度分别增加 56%及 2 .6倍。应用该氨基酸合剂使增高的尿 NAG活性减少 76% ,改善肾小管钠、钾排泄异常 ,增加 GFR 85%。结论 :溶酶体损伤可能在顺铂所致实验性 ARF发生极早期阶段起重要作用 ,氨基酸合剂有明显的肾功能保护作用 ,其机理可能通过改善受损的溶酶体功能所致。

Objective:To clarify the pathogenesis of cisplatin induced acute renal failure (ARF) and the nephroprotective effects and its possible mechanism of a mixture of 8 L amino acids.Methods: Animal model with nonoliguric ARF was established by an intravenous administration of 10 mg/kg cisplatin to male Sprague Dawley rats.A mixture of 8 L amino acids or 0.9% saline was infused at a rate of 2 ml/h for 3 h,starting with a 2 ml bolus injection before cisplatin administration.Urine N Acetylamino glucosaminidase (NAG),sodium and potassium concentrations and glomerular filtration rate (GFR) were measured.Morphological studies were also undertaken.Results:Thirty minutes after cisplatin injection,urine NAG excretion increased by 7.8 times;urine sodium and potassium concentrations increased by 56% and 2.6 times,respectively.The infusion of a mixture of 8 L amino acids increased GFR by 85% compared with control rats.The abnormalities of urine NAG,sodium and potassium excretion were markedly attenuated.The abnormal urine NAG excretion decreased by 76% compared with cisplatin treated animals.Conclusions:The present data suggest that:1.lysosomal autophagia may be a very early event in cisplatin induced ARF in rats;2.a mixture of 8 L amino acids shows a marked nephroprotection against experimental nonoliguric ARF;3.the amino acid mixture might function through inhibition of lysosomal autophagia in kidney tubules.