| 引用本文:王元元1,2，刘晓鹰2，李卉1，罗接红2，陈畅3，王林群1，张雪荣1，霍文丽2，陈雪莲2.基于代谢组学的幼龄大鼠血尿湿热证随时间变化规律的研究[J].世界中医药,2022,(16):. |
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| 基于代谢组学的幼龄大鼠血尿湿热证随时间变化规律的研究 |
| Time Variation of Hematuria Dampness-heat Syndrome in Juvenile Rats Based on Metabolomics |
| 投稿时间：2022-01-25 |
| DOI：10.3969/j.issn.1673-7202.2022.16.013 |
| 中文关键词: 孤立性血尿 湿热证 IgA肾病 代谢组学 时间点 血尿大鼠模型 |
| English Keywords:Isolated hematuria Dampness-heat syndrome IgA nephropathy Metabolomics Time node Hematuria rat model |
| 基金项目:国家自然科学基金面上项目（81473731）；湖北省卫生健康委中医药科研课题（2012Z-Y32） |
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| 中文摘要: |
| 目的：基于代谢组学NMR技术，寻找IgA肾病幼龄大鼠湿热证模型的标志性代谢物及相关代谢通路，为进一步药物干预寻找最佳时机提供理论依据。方法：选取72只3周龄雄性SD大鼠，按随机数字表法分为对照组和模型组，每组36只。构建大鼠IgA肾病模型。观察12周，每周大鼠称重并收集尿液，进行尿常规、代谢组学检测；第4、6、8、10、12各周采血进行生化指标、细胞因子、肾组织病理检测；代谢组学采用模式识别及多元变量统计学分析，筛选出可能的大鼠血尿湿热证标志物并建立相关代谢通路，比较一般情况、生化指标、细胞因子、肾组织病理等，探寻其时间变化规律。结果：与对照组比较，模型组：第5周起体质量增长速度放缓且出现湿热证候；尿检示第6周出现血尿，第8周出现蛋白尿；生化指标示TG、Chol、Scr均增高；肾组织病理示肾小球系膜区增殖性改变，实验第8、10、12周逐渐加重；免疫荧光可见IgA沉积；胞因子示核因子κB与转化生长因子-β1的表达分别自第6周、第10周起显著增高，与肾组织病理改变相对应；代谢组学判别出潜在的标志物14个，主要代谢路径6条，且随时间呈现一定的改变规律。结论：本实验初步探索出与中医血尿“湿热证”相关联的尿代谢组学的标志物及相应代谢通路，并提示尿代谢组学的改变早于生化、细胞因子、肾病理组织等其他微观层面，为进一步准确把握本病的干预时间点奠定了实验基础。 |
| English Summary: |
| To determine the landmark metabolites and related metabolic pathways of the dampness-heat syndrome model in juvenile rats with immunoglobulin A nephropathy(IgAN) based on NMR-based metabolomics,and provide a theoretical basis to seek the optimal timing for drug intervention.Methods:Seventy-two 3-week-old male SD rats were enrolled and divided into a control group and a model group according to a random number table,with 36 rats in each group.The IgAN model was replicated in rats.The rats were weighed and urine samples were collected every week for routine urine and metabolomics tests for 12 weeks.Blood samples were collected in the 4th,6th,8th,10th,and 12th weeks for biochemical indicators,cytokines,and renal histopathological detection.Pattern recognition and multivariate statistical analysis in metabolomics were employed to screen out potential markers of hematuria dampness-heat syndrome in rats and construct corresponding metabolic pathways.The general conditions,biochemical indicators,cytokines,renal histopathology,etc.were compared to explore the time variation law.Results:Compared with the control group,the model group showed slowed rate of weight gain and dampness-heat syndrome from the 5th week; blood urine in the 6th week and proteinuria in the 8th week; increased biochemical indicators,such as TG,Chol,and Scr; proliferative changes in the mesangial area of the glomerulus,which were gradually aggravated in the 8th,10th,and 12th weeks; IgA deposition as shown by immunofluorescence; increased expression of NF-κB and TGF-β1 from the 6th and 10th weeks respectively,corresponding to the pathological changes in renal tissues.Metabolomics identified 14 potential markers and six main metabolic pathways,which showed a certain change over time.Conclusion:This study preliminarily explored the urine metabolomics markers and corresponding metabolic pathways associated with hematuria dampness-heat syndrome in traditional Chinese medicine(TCM),and suggested that the changes in urine metabolomics were earlier than other microscopic levels such as biochemistry,cytokines,and renal pathology,which laid the experimental foundation for further accurately determining the optimal timing of intervention with this disease. |
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