摘要： 目的 探讨5-羟基-1-甲基海因（HMH）对百草枯（PQ）中毒所致肺损伤的保护作用及其机制。方法 采用随机数字法将30只SPF级小鼠分为生理盐水（NS）组、PQ组和HMH组，每组10只。取各组小鼠肺组织行代谢组学分析；切片并行HE染色，观察肺组织形态学改变；检测超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量；用Western blotting检测肺组织血红素氧合酶1（HO-1）蛋白表达情况。结果 光镜下，PQ组肺组织可见大量炎症细胞浸润，出血明显，肺泡腔透明膜形成；HMH组肺泡结构轻度损坏，少量炎症细胞渗出及出血。与NS组相比，PQ组和HMH组肺组织的MDA含量显著升高，SOD活性显著下降，PQ组HO-1蛋白表达增高；与PQ组相比，HMH组SOD活性及HO-1蛋白表达增高，MDA含量降低。与PQ组比较，HMH组N-乙酰天冬氨酸、谷氨酸、天冬氨酸等氨基酸含量增加；腺苷5'-磷酸、甲基丙二酸、胞嘧啶核苷、甲基富马酸升高；亚牛磺酸、苯甲酰S-二氧化物、磷酸乙酸含量升高；皮质甾酮、前列腺素G、4-吡哆酸、柠檬酸、黄嘌呤含量降低。结论 HMH能提升PQ中毒损伤肺组织的SOD活性，降低MDA水平，增加HO-1蛋白表达，并能纠正PQ导致的三羧酸循环紊乱，改善脂质过氧化，影响嘌呤、嘧啶和氨基酸的代谢。

5-羟基-1-甲基海因对百草枯中毒所致肺损伤保护作用的代谢组学研究

高利娜¹, 王光², 袁慧雅¹, 刘俊亭¹

1. 中国医科大学法医学院法医毒物分析教研室, 沈阳 110122;
2. 中国医科大学实验动物部, 沈阳 110122

收稿日期:2019-06-03出版日期:2020-08-30发布日期:2020-08-04
通讯作者:刘俊亭E-mail:jtliu@cmu.edu.cn
作者简介:高利娜(1983-),女,副教授,博士.
基金资助:国家自然科学基金（81601644，81671864）


关键词: 百草枯, 中毒, 5-羟基-1-甲基海因, 代谢组学
Abstract: Objective To investigate the protective effect of the compound 5-hydroxy-1-methylhydantoin (HMH) against lung injury induced by paraquat (PQ) poisoning. Methods Thirty SPF healthy Kunming mice were randomly divided into the normal saline (NS) control group,PQ poisoning model group,and HMH intervention group. The lung tissues were dissected for metabolomics analysis and HE staining. Superoxide dismutase (SOD) activity,malondialdehyde (MDA) content,and heme oxygenase-1 (HO-1) expression levels in lung tissues were measured. Results A large number of inflammatory cells appeared to be infiltrated with obvious bleeding and clear membrane formation in the alveolar cavity of the PQ group mice. The alveolar structures of the HMH group mice were damaged slightly with exudation of small amounts of inflammatory cells resulting in hemorrhage. Compared with the NS control group,the contents of MDA and HO-1 were significantly increased in the PQ group mice,while the SOD activity of lung tissues was significantly decreased. Also,in comparison to the PQ group mice,the SOD activity and HO-1 were increased and the MDA content was decreased in the HMH group mice. Finally,in comparison to the PQ group,the contents of metabolites,such as,N-acetyl aspartic acid,glutamic acid,aspartic acid,adenosine 5'-monophosphate,methylmalonic acid,cytidine,mesaconic acid,hypotaurine,thiobenzamide-S,S-dioxide,and phosphonoacetic acid were increased,while the contents of corticosterone,prostaglandin G2,4-pyridoxic acid,citric acid,and xanthine were decreased in the HMH group. Conclusion HMH treatment enhances the SOD activity,elevates HO-1 levels,and reduces the content of MDA present in the lung tissues damaged by PQ. Also,HMH could correct the disturbances in the tricarboxylic acid cycle caused by PQ poisoning and improve lipid peroxidation rates,and this in turn could affect the metabolisms of purines,pyrimidines,and amino acids.
Key words: paraquat, poisoning, 5-hyroxy-1-methylhydantoin, metabolomics
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