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  • 朱旷旷,谢建絮,余海波,等.急性百草枯中毒小鼠氨基酸代谢特点[J].同济大学学报(医学版),2021,42(5):604-611.    [点击复制]
  • ZHU Kuang-kuang,XIE Jian-xu,YU Hai-bo,et al.The characteristics of amino acid metabolism in mice with acute paraquat poisoning[J].同济大学学报(医学版),2021,42(5):604-611.   [点击复制]
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急性百草枯中毒小鼠氨基酸代谢特点
朱旷旷,谢建絮,余海波,彭艾
0
(同济大学附属第十人民医院肾脏风湿科,上海200072)
摘要:
目的探究百草枯(Paraquat, PQ)中毒小鼠氨基酸代谢特点及其与肝肾功能的关系。方法将30只小鼠随机分为对照组(n=10)、PQ中毒4 h组(n=10)和PQ中毒48 h组(n=10),分别检测各组小鼠血肌酐(serum creatinine, SCr)、血尿素氮(blood urea nitrogen, BUN)、谷草转氨酶(aspartate aminotransferase, AST)、谷丙转氨酶(alanine transaminase, ALT);靶向代谢组学检测对照组、PQ中毒4 h组小鼠血浆与肝氨基酸水平。采用主成分分析和正交偏最小二乘-判别分析判断各组氨基酸组成相似性;Spearman分析差异氨基酸与肝肾功能相关性。结果PQ中毒4 h组BUN显著降低(P=0.009),AST、ALT均显著增高(P=0.001,P=0.023);PQ中毒48 h组BUN显著增高(P=0.033);PQ中毒4 h后血浆亮氨酸、异亮氨酸、缬氨酸、色氨酸、苯丙氨酸、牛磺酸显著上调,蛋氨酸显著下调(均P<0.05)。亮氨酸、色氨酸、缬氨酸、异亮氨酸、苯丙氨酸、牛磺酸与AST显著正相关(均P<0.05);亮氨酸、缬氨酸、异亮氨酸、苯丙氨酸、牛磺酸与ALT显著正相关(均P<0.05);异亮氨酸、亮氨酸与SCr显著负相关(均P<0.05),蛋氨酸与BUN显著正相关(P<0.01)。结论PQ中毒小鼠的氨基酸代谢发生显著改变,其中,牛磺酸、缬氨酸、亮氨酸、苯丙氨酸、色氨酸、异亮氨酸、蛋氨酸可作为早期诊断PQ中毒及评估肝肾功能的生物标志物。
关键词:  百草枯中毒  氨基酸代谢  靶向代谢组学  肝功能  肾功能
DOI:10.12289/j.issn.1008-0392.21111
投稿时间:2021-03-24
基金项目:国家自然科学基金面上项目(81971822)
The characteristics of amino acid metabolism in mice with acute paraquat poisoning
ZHU Kuang-kuang,XIE Jian-xu,YU Hai-bo,PENG Ai
(Dept. of Nephrology & Rheumatology, Shanghai Tenth Peoples Hospital, School of Medicine, Tongji University, Shanghai 200072, China)
Abstract:
ObjectiveTo explore the characteristics of amino acid metabolism in mice with paraquat(PQ) poisoning and its relationship with liver and kidney function. MethodsThirty SPF C57BL/6J mice were randomly divided into control group, PQ poisoning 4 h group and PQ poisoning 48 h group with 10 mice in each group. The blood creatinine(SCr), urea nitrogen(BUN), aspartate aminotransferase(AST), alanine transaminase(ALT) levels were measured. Targeted metabolomics was performed to detect plasma and liver amino acid levels in control and PQ poisoning 4h groups. Principal component analysis and orthogonal partial least squares-discriminant analysis were used to judge the similarity of amino acid composition in each group. Spearman analysis was used to analyze the correlation between different amino acids and liver, kidney function. ResultsIn the PQ poisoning 4 h group, BUN was significantly decreased(P=0.009), and AST and ALT were significantly increased(P=0.001, P=0.023). BUN increased significantly in the PQ poisoning 48 h group(P=0.033). Plasma leucine, isoleucine, valine, tryptophan, phenylalanine, taurine in PQ poisoning 4 h group was significantly increased, and methionine was significantly decreased(all P<0.05). Leucine, tryptophan, valine, isoleucine, phenylalanine and taurine levels were positively correlated with AST(all P<0.05); lucine, valine, isoleucine, phenylalanine and taurine levels were positively correlated with ALT(all P<0.05). Isoleucine and leucine were negatively correlated with SCr(all P<0.05), and methionine was positively correlated with BUN(P<0.01). ConclusionThe amino acid metabolism changes significantly in PQ poisoning mice; and the plasma taurine, valine, leucine, phenylalanine, tryptophan, isoleucine and methionine can be used as biomarkers for early diagnosis of PQ poisoning and the evaluation of liver and kidney function.
Key words:  paraquat poisoning  amino acid metabolism  targeted metabolomics  liver function  kidney function

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